玻璃体腔接种视网膜S抗原诱导的免疫偏离
作者：李志杰 彭广华 冯 铮 李辰
单位：广州暨南大学组织移植与免疫实验中心，眼科学教研室(广州 510632)
关键词：免疫性；抗原；玻璃体；视网膜；白细胞介素-1
Immune deviation elicited by retinal S antigen injected into the vitreous cavity Immune deviation elicited by retinal S antigen injected
into the vitreous cavity*
LI Zhi-Jie, PENG Guang-Hua, FENG Zheng, LI Chen
, http://www.100md.com
Department of Ophthalmology, Institute of Tissue Transplantation & Immunology,Jinan University, Guangzhou (510632)
Abstract AIM：To determine whether the vitreous cavity (VC) is capable of supporting the induction of deviant immune response to retinal soluble (S) antigen and to observe the influence of interleukin-1 (IL-1) on the immunologic properties of the VC. METHODS： Retinal S antigen was inoculated into the anterior chamber (AC) and VC in Wistar rats. Seven days after antigen inoculation, the recipient animals were immunized with S antigen and complete Freund's adjuvant. Delayed-type hypersensitivity (DTH) was then assessed by footpad challenge. To alter systemic immune conditions, IL-1 was administrated by intraperitoneal injection. RESULTS： Antigen-specific DTH did not develop in rats in which S antigen was injected into the AC and the VC. In contrast, strong DTH was elicited by S antigen injected into the AC and VC if IL-1 was administrated systemically for 7 consecutive days after the antigen challenge. CONCLUSION： The VC is capable of supporting immune deviation to soluble antigen by actively suppressing antigen-specific DTH. Systemic administration of exogenous IL-1 eliminates the capacity of the VC to support immune deviation inducing by soluble antigen injected locally.
, 百拇医药
MeSH Immunity; Antigens; Vitreous body; Retina;Interleukin-1
摘 要 目的：确立玻璃体腔(VC)是否具有支持针对视网膜可溶性抗原(S抗原)刺激诱导偏离式免疫反应的能力，并观察白细胞介素-1(IL-1)对玻璃体腔免疫特性的影响。方法：将视网膜S抗原接种于Wistar大鼠的眼前房和玻璃体腔。抗原接种后7 d，使用S抗原和完全福氏佐剂免疫受主动物。然后，通过足部刺激评估迟发型超敏反应(DTH)。通过腹腔注射IL-1改变全身的免疫状态。结果：前房和玻璃体腔注射S抗原的动物没有发生抗原特异性DTH。与此相反，当全身给予IL-1时，注射于前房和玻璃体腔的S抗原则激发剧烈的DTH。结论：玻璃体腔具有通过抑制抗原特异性DTH，支持针对可溶性抗原的免疫偏离的诱导能力。全身使用外源性IL-1可以消除玻璃体腔针对局部接种可溶性抗原诱导免疫偏离的能力。
Antigenic material introduced into the anterior chamber (AC) is not ignored by the systemic immune apparatus. Instead, intraocular antigen elicits a stereotypic, systemic immune response that is selectively deficient in T cells that mediate delayed-type hypersensitivity (DTH). At the same time, other types of T cells are activated, including regulatory T cells and precursors of cytotoxic T cells. This deviant form of systemic immunity was termed anterior chamber-associated immune deviation (ACAID). Current evidence indicates that ACAID is the central feature of ocular immune privilege. It is only within the latest 25 years that ACAID has been studied in detail[1]. So far, however only a few studies concerning immune deviation elicited by antigens injected into the posterior part of the eye have been reported[2,3]. The aim of present study is to determine whether a deviant immune response similar to ACAID may also be induced by injection of soluble antigens into the vitreous cavity (VC). In addition, we scheduled to observe effect of interleukin-1 (IL-1) on the capacity of the VC to induce antigen-specific immune deviation because IL-1 is a key immunomodulator shown to trigger many events of the inflammatory response.
, http://www.100md.com
MATERIALS AND METHEODS
Animals： Adult male Wistar rats were used throughout this study. Inoculations, injections and clinical examinations were conducted in animals under general anesthesia induced by intramuscular injection of 25mg/kg ketamine and 25mg/kg chlorpromazine.
Retinal soluble antigen： S antigen was prepared from bovine retinas by hypotonic buffer extraction followed by 50% ammonium sulfate precipitation, gel filtration, and ion exchange chromatography as described previously [4].
, 百拇医药
Intraocular antigen inoculation： For AC injection, an oblique transcorneal paracentesis was performed with a microinjector under the microscope, and 100 μg S of antigen in 10 μL of phosphate-buffered saline (PBS) were injected. For VC injection, an paracentesis was made at the pars plana and 100 μg S of antigen in 10 μL of PBS were introduced into the center of the vitreous cavity[5].
DTH assay： Seven days after the intraocular inoculation of S antigen, animals were immunized subcutaneously with 100 μg of S antigen and complete Freund's adjuvant (CFA, Sigma). Footpad-swelling analysis was performed 7 days later. DTH was measured as previously described[5]. Briefly, 100μg of S antigen in 10 μL of PBS solution were injected into the left posterior footpad of the rat. The right posterior footpad serving as unchallenged control was injected with PBS alone. Footpad swelling was measured 24 hours later with an engineer's micrometer. Units of swelling were determined by the difference in thickness between the challenged left footpad and the unchallenged control right footpad of the animals.
, http://www.100md.com
Exogenous IL-1 administration： A single daily dose of 10 units of human recombinant IL-1(hrIL-1) in 10 μL of PBS was delivered to each animal by intraperitoneal injection for 7 consecutive days after VC inoculation of antigen. Control animals received each a daily intraperitoneal injection of 10 μL of PBS.
Statistics： The Student t-test was used to test for the statistical validity of the data.
RESULTS
, http://www.100md.com
Immune deviation induced by soluble antigen in the anterior chamber and the vitreous cavity：After injection of S antigen into the AC and the VC, animals were immunized with S antigen and CFA at day 7. Evaluation by footpad challenge was performed 7 days later. No DTH was detectable in animals that had been given intraocular injection (AC or VC) of S antigen. By contrast, animals immunized with S antigen-CFA without previous intraocular injection of S antigen displayed intense DTH (Fig 1).
, 百拇医药
Fig 1 Delayed-type hypersensitivity measurements after inoculation of S antigen into different ocular sites. Footpad swelling analysis was performed 24 hours after footpad challenge with S antigen in animals with inoculation of S antigen into the anterior chamber (AC) or the vitreous cavity (VC). Negative control animals (Naive) were not immunized. Positive control animals (P)were immunized only. * P<0.05,vs positive control animals.
Effect of IL-1 on the immune deviation induced by S antigen in the anterior chamber and the vitreous cavity： As reported by Benson et al[6], IL-1 administration compromised the capability of the AC to support immune deviation by soluble antigen injected locally. Thus, our assumption is that IL-1 may also abrogate the immune deviation induced by antigen inoculated into the vitreous cavity. To determine whether IL-1 has a disruptive effect on the immune privilege of the VC, IL-1 was administrated by intraperitoneal injection for 7 days after S antigen had been inoculated into the VC. When S antigen was injected into the eyes of the rats treated with IL-1, the recipients mounted strong DTH response; that is, they displayed no immune deviation (Fig 2).
, http://www.100md.com
Fig 2 Delayed-type hypersensitivity measurements after intraocular inoculation of S antigen with and without treatment with interleukin-1. Footpad swelling analysis was performed 24 hours after footpad challenge with S antigen in animals with inoculation of S antigen into the anterior chamber (AC) or the vitreous cavity (VC). Groups of animals with inoculation of S antigen into the anterior chamber (AC) or the vitreous cavity (VC) received systemic administration of interleukin-1 (AC/SI; VC/SI) after intraocular inoculation of antigen. Negative control animals (N) were not immunized. Positive control animals (P) were immunized only. * P<0.05, vs positive control animals
, 百拇医药
DISCUSSION
The results of experiments show that, similar to the anterior chamber, the vitreous cavity is also an immunologically privileged site for soluble antigens. After injection of the antigen into the vitreous cavity, the corresponding specific DTH is suppressed. The feature discovered so far resemble those of the AC: antigen-specific DTH expression was suppressed and immune deviation was abrogated by IL-1 administration. However, there are definitely immune differences between the AC and the vitreous cavity. Recently, we analyzed the metabolic pathways of [125?I] labeled soluble antigen in the AC and the vitreous cavity, and found that the soluble antigen was released into the blood through the ocular posterior parts instead of the anterior chamber (unpublished data). Thus, it seems that the antigen-bearing signals from the vitreous cavity responsible for immune deviation are likely to escape through the choroid and therefore travel via the lymph vessels to the cervical lymph nodes. Egan et al[7] reported T-cell expansion in the draining lymph nodes after intravitreal inoculation of antigen. In addition, they found a greater T-cell expansion within the periarteriolar lymphoid sheaths of the spleen in VC injected mice, as compared with that in mice immunized through the conventional route. Whether these findings indicate differences between immune deviation induced by the AC and the vitreous cavity of the eye awaits further investigation.
, http://www.100md.com
Ocular immune privilege is regulated by multiple factors, both locally and systemically[5]. To test the influence of changing systemic immune status, we injected IL-1 after intraocular inoculation of antigen. It was demonstrated that intraperitoneal injection of IL-1 after antigen inoculation into the vitreous cavity could abrogate the immune deviation induced by soluble antigen in the vitreous cavity. What are the mechanisms by which IL-1 abrogates immune privilege? One possible explanation is that IL-1 may directly or indirectly alter the host's immune status. IL-1 is a potent immunomodulator and has been shown to initiate many events of the inflammatory response. The biologic effects of IL-1 depend on the quantity of the cytokine released. When released in large amounts, IL-1 enters the blood stream and exerts endocrine effects. IL-1 administered systemically shares with TNF the capability to cause fever, to induce synthesis of acute phase plasma proteins by the liver, and to trigger metabolic wasting[8]. IL-1 also plays a critical role in initiating immune responses by virtue of its action on the function of antigen presenting cells (APC). IL-1 can significantly augment the accessory function of APCs to sensitize T cells.
, 百拇医药
Another possible reason for sustained loss of immune privilege of the vitreous cavity after IL-1 administration may be changes in the ocular microenvironment. At low concentrations, IL-1 mainly functions as a mediator of local inflammation. For example, IL-1 acts on endothelial cells to promote coagulation, and increases expression of surface molecules that mediate leukocyte adhesion, and activates perivascular macrophages. Numerous studies have shown that intraocular administration resulted in dramatic ocular inflammation and breakdown of the blood-ocular barrier[9]. Besides, IL-1 acts in synergy with other cytokines to enhance IL-6 and IL-8 expression by retinal pigment epithelial cells[10]. Chemokines like IL-6 and IL-8 can act on leukocytes to promote their extravasation[8]. However, the concentration of IL-1 actually reaching the posterior part of the eye after intraperitoneal injection of the cytokine has not been determined. So far, systemic administration of IL-1 has not been shown to be associated with ocular inflammation, nor have patients with high circulating cytokine levels been reported to develop ocular complications. Thus, the direct effect of systemically administrated IL-1 on the immunoregulatory mechanisms in the eye remains to be explored.
, 百拇医药
Based on the results of the present study and the findings of others[3], we infer that the vitreous cavity may be an immune-privileged site. Immune deviation induced by inoculation of retinal-specific antigens into the vitreous cavity may represent a physiologic mechanism designed to prevent activation of immunopathogenic effectors that recognize intraocular antigens. Penetrating trauma to the retina may result in the release of immunogenic molecules from the retina, which is an event similar to intraocular inoculation of retinal antigens. In this circumstance, immunogenic molecules would be expected to induce antigen-specific immune deviation that would have the effect of preventing, rather than promoting autoimmune retinitis. We have recently found that the intraocular inoculation of retinal antigens into the vitreous cavity led to a significant suppression of intraocular inflammation in the rat model of antigen-induced uveitis (unpublished data). Thus, the immunologic mechanisms and the potential applicability of the induction of immune deviation associated with the vitreous cavity merit further study.
, 百拇医药
* Project supported by the National Natural Science Foundation of China (No:39500158), Huo Yingdong Education Foundation in Ministry of Education, the and Natural Science Foundation of Guangdong Province (No:960208)
REFERENCES
1 Streilein JW. Immunoregulatory mechanisms of the eye. Prog Ret Eye Res， 1999， 18:357.
2 Tsumura K, Watanabe M, Sakata H. Cytotoxic T lymphocyte activity after intravitreous inoculation of herpes simplex virus type I in mice. Ophthalmol Res， 1995， 27:32.
, 百拇医药
3 Jiang LQ, Streilein JW. Immune privilege extended to allogeneic tumor cells in the vitreous cavity. Invest Ophthalmol Vis Sci， 1991， 32:224.
4 Chen J, Li Z, Li C. Simple and rapid method for isolation of retinal S antigen. Chin Ophthal Res, 1998, 16:96.
5 Li Z, Peng G, Li C. Anterior chamber-associated immune deviation during normal pregnancy in rabbits. Chin Ophthal Res, 1996, 17:161.
6 Benson JL, Niederkorn JY. Interleukin-1 abrogates anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci, 1990, 31: 2123.
, 百拇医药
7 Egan RM, Yorkey C, Black R, et al. Peptide-specific T cell clonal expression in vivo following immunization in the eye, an immune-privileged site. J Immunol, 1996, 157:2262.
8 Abbas AK, Lightman AH, Pober JS. Cellular and molecular immunology. 3rd ed. Philadelphia: W. B. Sauders Company, 1997. 249.
9 Kijlstra A. Cytokines: their role in uveal disease. Eye, 1997, 11:200.
10 Kuppner MC, McKillop-Smith S, Forrester JV. TGF-beta and IL-1 beta act in synergy to enhance human retinal pigment epithelial cells. Immunology， 1995， 84:265.
(Received 1999-05-26,Accepted 1999-07-02), 百拇医药
单位：广州暨南大学组织移植与免疫实验中心，眼科学教研室(广州 510632)
关键词：免疫性；抗原；玻璃体；视网膜；白细胞介素-1
Immune deviation elicited by retinal S antigen injected into the vitreous cavity Immune deviation elicited by retinal S antigen injected
into the vitreous cavity*
LI Zhi-Jie, PENG Guang-Hua, FENG Zheng, LI Chen
, http://www.100md.com
Department of Ophthalmology, Institute of Tissue Transplantation & Immunology,Jinan University, Guangzhou (510632)
Abstract AIM：To determine whether the vitreous cavity (VC) is capable of supporting the induction of deviant immune response to retinal soluble (S) antigen and to observe the influence of interleukin-1 (IL-1) on the immunologic properties of the VC. METHODS： Retinal S antigen was inoculated into the anterior chamber (AC) and VC in Wistar rats. Seven days after antigen inoculation, the recipient animals were immunized with S antigen and complete Freund's adjuvant. Delayed-type hypersensitivity (DTH) was then assessed by footpad challenge. To alter systemic immune conditions, IL-1 was administrated by intraperitoneal injection. RESULTS： Antigen-specific DTH did not develop in rats in which S antigen was injected into the AC and the VC. In contrast, strong DTH was elicited by S antigen injected into the AC and VC if IL-1 was administrated systemically for 7 consecutive days after the antigen challenge. CONCLUSION： The VC is capable of supporting immune deviation to soluble antigen by actively suppressing antigen-specific DTH. Systemic administration of exogenous IL-1 eliminates the capacity of the VC to support immune deviation inducing by soluble antigen injected locally.
, 百拇医药
MeSH Immunity; Antigens; Vitreous body; Retina;Interleukin-1
摘 要 目的：确立玻璃体腔(VC)是否具有支持针对视网膜可溶性抗原(S抗原)刺激诱导偏离式免疫反应的能力，并观察白细胞介素-1(IL-1)对玻璃体腔免疫特性的影响。方法：将视网膜S抗原接种于Wistar大鼠的眼前房和玻璃体腔。抗原接种后7 d，使用S抗原和完全福氏佐剂免疫受主动物。然后，通过足部刺激评估迟发型超敏反应(DTH)。通过腹腔注射IL-1改变全身的免疫状态。结果：前房和玻璃体腔注射S抗原的动物没有发生抗原特异性DTH。与此相反，当全身给予IL-1时，注射于前房和玻璃体腔的S抗原则激发剧烈的DTH。结论：玻璃体腔具有通过抑制抗原特异性DTH，支持针对可溶性抗原的免疫偏离的诱导能力。全身使用外源性IL-1可以消除玻璃体腔针对局部接种可溶性抗原诱导免疫偏离的能力。
Antigenic material introduced into the anterior chamber (AC) is not ignored by the systemic immune apparatus. Instead, intraocular antigen elicits a stereotypic, systemic immune response that is selectively deficient in T cells that mediate delayed-type hypersensitivity (DTH). At the same time, other types of T cells are activated, including regulatory T cells and precursors of cytotoxic T cells. This deviant form of systemic immunity was termed anterior chamber-associated immune deviation (ACAID). Current evidence indicates that ACAID is the central feature of ocular immune privilege. It is only within the latest 25 years that ACAID has been studied in detail[1]. So far, however only a few studies concerning immune deviation elicited by antigens injected into the posterior part of the eye have been reported[2,3]. The aim of present study is to determine whether a deviant immune response similar to ACAID may also be induced by injection of soluble antigens into the vitreous cavity (VC). In addition, we scheduled to observe effect of interleukin-1 (IL-1) on the capacity of the VC to induce antigen-specific immune deviation because IL-1 is a key immunomodulator shown to trigger many events of the inflammatory response.
, http://www.100md.com
MATERIALS AND METHEODS
Animals： Adult male Wistar rats were used throughout this study. Inoculations, injections and clinical examinations were conducted in animals under general anesthesia induced by intramuscular injection of 25mg/kg ketamine and 25mg/kg chlorpromazine.
Retinal soluble antigen： S antigen was prepared from bovine retinas by hypotonic buffer extraction followed by 50% ammonium sulfate precipitation, gel filtration, and ion exchange chromatography as described previously [4].
, 百拇医药
Intraocular antigen inoculation： For AC injection, an oblique transcorneal paracentesis was performed with a microinjector under the microscope, and 100 μg S of antigen in 10 μL of phosphate-buffered saline (PBS) were injected. For VC injection, an paracentesis was made at the pars plana and 100 μg S of antigen in 10 μL of PBS were introduced into the center of the vitreous cavity[5].
DTH assay： Seven days after the intraocular inoculation of S antigen, animals were immunized subcutaneously with 100 μg of S antigen and complete Freund's adjuvant (CFA, Sigma). Footpad-swelling analysis was performed 7 days later. DTH was measured as previously described[5]. Briefly, 100μg of S antigen in 10 μL of PBS solution were injected into the left posterior footpad of the rat. The right posterior footpad serving as unchallenged control was injected with PBS alone. Footpad swelling was measured 24 hours later with an engineer's micrometer. Units of swelling were determined by the difference in thickness between the challenged left footpad and the unchallenged control right footpad of the animals.
, http://www.100md.com
Exogenous IL-1 administration： A single daily dose of 10 units of human recombinant IL-1(hrIL-1) in 10 μL of PBS was delivered to each animal by intraperitoneal injection for 7 consecutive days after VC inoculation of antigen. Control animals received each a daily intraperitoneal injection of 10 μL of PBS.
Statistics： The Student t-test was used to test for the statistical validity of the data.
RESULTS
, http://www.100md.com
Immune deviation induced by soluble antigen in the anterior chamber and the vitreous cavity：After injection of S antigen into the AC and the VC, animals were immunized with S antigen and CFA at day 7. Evaluation by footpad challenge was performed 7 days later. No DTH was detectable in animals that had been given intraocular injection (AC or VC) of S antigen. By contrast, animals immunized with S antigen-CFA without previous intraocular injection of S antigen displayed intense DTH (Fig 1).
, 百拇医药
Fig 1 Delayed-type hypersensitivity measurements after inoculation of S antigen into different ocular sites. Footpad swelling analysis was performed 24 hours after footpad challenge with S antigen in animals with inoculation of S antigen into the anterior chamber (AC) or the vitreous cavity (VC). Negative control animals (Naive) were not immunized. Positive control animals (P)were immunized only. * P<0.05,vs positive control animals.
Effect of IL-1 on the immune deviation induced by S antigen in the anterior chamber and the vitreous cavity： As reported by Benson et al[6], IL-1 administration compromised the capability of the AC to support immune deviation by soluble antigen injected locally. Thus, our assumption is that IL-1 may also abrogate the immune deviation induced by antigen inoculated into the vitreous cavity. To determine whether IL-1 has a disruptive effect on the immune privilege of the VC, IL-1 was administrated by intraperitoneal injection for 7 days after S antigen had been inoculated into the VC. When S antigen was injected into the eyes of the rats treated with IL-1, the recipients mounted strong DTH response; that is, they displayed no immune deviation (Fig 2).
, http://www.100md.com
Fig 2 Delayed-type hypersensitivity measurements after intraocular inoculation of S antigen with and without treatment with interleukin-1. Footpad swelling analysis was performed 24 hours after footpad challenge with S antigen in animals with inoculation of S antigen into the anterior chamber (AC) or the vitreous cavity (VC). Groups of animals with inoculation of S antigen into the anterior chamber (AC) or the vitreous cavity (VC) received systemic administration of interleukin-1 (AC/SI; VC/SI) after intraocular inoculation of antigen. Negative control animals (N) were not immunized. Positive control animals (P) were immunized only. * P<0.05, vs positive control animals
, 百拇医药
DISCUSSION
The results of experiments show that, similar to the anterior chamber, the vitreous cavity is also an immunologically privileged site for soluble antigens. After injection of the antigen into the vitreous cavity, the corresponding specific DTH is suppressed. The feature discovered so far resemble those of the AC: antigen-specific DTH expression was suppressed and immune deviation was abrogated by IL-1 administration. However, there are definitely immune differences between the AC and the vitreous cavity. Recently, we analyzed the metabolic pathways of [125?I] labeled soluble antigen in the AC and the vitreous cavity, and found that the soluble antigen was released into the blood through the ocular posterior parts instead of the anterior chamber (unpublished data). Thus, it seems that the antigen-bearing signals from the vitreous cavity responsible for immune deviation are likely to escape through the choroid and therefore travel via the lymph vessels to the cervical lymph nodes. Egan et al[7] reported T-cell expansion in the draining lymph nodes after intravitreal inoculation of antigen. In addition, they found a greater T-cell expansion within the periarteriolar lymphoid sheaths of the spleen in VC injected mice, as compared with that in mice immunized through the conventional route. Whether these findings indicate differences between immune deviation induced by the AC and the vitreous cavity of the eye awaits further investigation.
, http://www.100md.com
Ocular immune privilege is regulated by multiple factors, both locally and systemically[5]. To test the influence of changing systemic immune status, we injected IL-1 after intraocular inoculation of antigen. It was demonstrated that intraperitoneal injection of IL-1 after antigen inoculation into the vitreous cavity could abrogate the immune deviation induced by soluble antigen in the vitreous cavity. What are the mechanisms by which IL-1 abrogates immune privilege? One possible explanation is that IL-1 may directly or indirectly alter the host's immune status. IL-1 is a potent immunomodulator and has been shown to initiate many events of the inflammatory response. The biologic effects of IL-1 depend on the quantity of the cytokine released. When released in large amounts, IL-1 enters the blood stream and exerts endocrine effects. IL-1 administered systemically shares with TNF the capability to cause fever, to induce synthesis of acute phase plasma proteins by the liver, and to trigger metabolic wasting[8]. IL-1 also plays a critical role in initiating immune responses by virtue of its action on the function of antigen presenting cells (APC). IL-1 can significantly augment the accessory function of APCs to sensitize T cells.
, 百拇医药
Another possible reason for sustained loss of immune privilege of the vitreous cavity after IL-1 administration may be changes in the ocular microenvironment. At low concentrations, IL-1 mainly functions as a mediator of local inflammation. For example, IL-1 acts on endothelial cells to promote coagulation, and increases expression of surface molecules that mediate leukocyte adhesion, and activates perivascular macrophages. Numerous studies have shown that intraocular administration resulted in dramatic ocular inflammation and breakdown of the blood-ocular barrier[9]. Besides, IL-1 acts in synergy with other cytokines to enhance IL-6 and IL-8 expression by retinal pigment epithelial cells[10]. Chemokines like IL-6 and IL-8 can act on leukocytes to promote their extravasation[8]. However, the concentration of IL-1 actually reaching the posterior part of the eye after intraperitoneal injection of the cytokine has not been determined. So far, systemic administration of IL-1 has not been shown to be associated with ocular inflammation, nor have patients with high circulating cytokine levels been reported to develop ocular complications. Thus, the direct effect of systemically administrated IL-1 on the immunoregulatory mechanisms in the eye remains to be explored.
, 百拇医药
Based on the results of the present study and the findings of others[3], we infer that the vitreous cavity may be an immune-privileged site. Immune deviation induced by inoculation of retinal-specific antigens into the vitreous cavity may represent a physiologic mechanism designed to prevent activation of immunopathogenic effectors that recognize intraocular antigens. Penetrating trauma to the retina may result in the release of immunogenic molecules from the retina, which is an event similar to intraocular inoculation of retinal antigens. In this circumstance, immunogenic molecules would be expected to induce antigen-specific immune deviation that would have the effect of preventing, rather than promoting autoimmune retinitis. We have recently found that the intraocular inoculation of retinal antigens into the vitreous cavity led to a significant suppression of intraocular inflammation in the rat model of antigen-induced uveitis (unpublished data). Thus, the immunologic mechanisms and the potential applicability of the induction of immune deviation associated with the vitreous cavity merit further study.
, 百拇医药
* Project supported by the National Natural Science Foundation of China (No:39500158), Huo Yingdong Education Foundation in Ministry of Education, the and Natural Science Foundation of Guangdong Province (No:960208)
REFERENCES
1 Streilein JW. Immunoregulatory mechanisms of the eye. Prog Ret Eye Res， 1999， 18:357.
2 Tsumura K, Watanabe M, Sakata H. Cytotoxic T lymphocyte activity after intravitreous inoculation of herpes simplex virus type I in mice. Ophthalmol Res， 1995， 27:32.
, 百拇医药
3 Jiang LQ, Streilein JW. Immune privilege extended to allogeneic tumor cells in the vitreous cavity. Invest Ophthalmol Vis Sci， 1991， 32:224.
4 Chen J, Li Z, Li C. Simple and rapid method for isolation of retinal S antigen. Chin Ophthal Res, 1998, 16:96.
5 Li Z, Peng G, Li C. Anterior chamber-associated immune deviation during normal pregnancy in rabbits. Chin Ophthal Res, 1996, 17:161.
6 Benson JL, Niederkorn JY. Interleukin-1 abrogates anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci, 1990, 31: 2123.
, 百拇医药
7 Egan RM, Yorkey C, Black R, et al. Peptide-specific T cell clonal expression in vivo following immunization in the eye, an immune-privileged site. J Immunol, 1996, 157:2262.
8 Abbas AK, Lightman AH, Pober JS. Cellular and molecular immunology. 3rd ed. Philadelphia: W. B. Sauders Company, 1997. 249.
9 Kijlstra A. Cytokines: their role in uveal disease. Eye, 1997, 11:200.
10 Kuppner MC, McKillop-Smith S, Forrester JV. TGF-beta and IL-1 beta act in synergy to enhance human retinal pigment epithelial cells. Immunology， 1995， 84:265.
(Received 1999-05-26,Accepted 1999-07-02), 百拇医药