Detection of S-antigen presenting cells in experimental autoimmune uveitis by bone marrow chimeras

S. Ishimoto, V. Gullapalli, Jie Zhang, N. A. Rao

Research output: Contribution to journalArticle

Abstract

Purpose. The importance of organ-specific, T cell-mediated autoimmunity has been shown in experimental autoimmune uveitis (EAU); however, there is no clear understanding about local autoantigen presentation to organ-specific T cells in the eye. We previously demonstrated with an in vivo study using bone marrow chimeras that hematopoietically derived cells in the retina can present retinal antigen to uveitogenic CD4+ T cells in the development of EAU. In contrast, in vitro studies have suggested retinal resident cells such as retinal pigment epithelium, vascular endothelium or possibly glial cells may function as antigen-presenting cells. The purpose of this study is to investigate the role of these retinal cells in antigen presentation in vivo and in the development of uveitis. Methods. (Lewis x Brown Norway)F1 [LBN/F1(RT-1l/n)] rats were made chimeric after lethal whole-body irradiation by transplanting 50x106 bone marrow cells from Brown Norway [BN(RT-1n)] donors. Three months after reconstitution, three rats of each groups; chimeric, Lewis [LEW(RT-11)], LBN/F1 and BN rats, were each given 15x106 S-antigen specific CD4+ LBN/F1 T cells by intracardiac injection. Highly purified CD4+ T cells were obtained and were confirmed by FACS analysis. MHC class II restriction was determined by a proliferation assay. All animals were sacrificed on the ninth day after adoptive transfer and the eyes were evaluated histologically. Results. All LEW and LBN/F1 rats showed typical features of EAU but none of chimeric rats developed the uveitis and BN rat eyes were normal. LBN/F1 CD4+ T cells were restricted only by LEW(RT-11). Conclusions. The failure of the chimeras to develop the uveitis with transfer of LEW-specific, MHC class II-restricted, uveitogenic T cells indicates that none of the retinal/uveal resident cells (with the exception of bone marrow derived cells) present S-antigen in the induction of EAU. Based on the present and previous studies it appears that bone marrow-derived cells are required for S-antigen presentation in vivo for the initiation of EAU.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

Fingerprint

Uveitis
Antigen-Presenting Cells
Bone Marrow
T-Lymphocytes
Inbred BN Rats
Bone Marrow Cells
Antigen Presentation
Norway
Antigens
CD4 Antigens
Adoptive Transfer
Retinal Pigment Epithelium
Whole-Body Irradiation
Vascular Endothelium
Autoimmunity
Neuroglia
Retina
Injections

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Detection of S-antigen presenting cells in experimental autoimmune uveitis by bone marrow chimeras. / Ishimoto, S.; Gullapalli, V.; Zhang, Jie; Rao, N. A.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

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N2 - Purpose. The importance of organ-specific, T cell-mediated autoimmunity has been shown in experimental autoimmune uveitis (EAU); however, there is no clear understanding about local autoantigen presentation to organ-specific T cells in the eye. We previously demonstrated with an in vivo study using bone marrow chimeras that hematopoietically derived cells in the retina can present retinal antigen to uveitogenic CD4+ T cells in the development of EAU. In contrast, in vitro studies have suggested retinal resident cells such as retinal pigment epithelium, vascular endothelium or possibly glial cells may function as antigen-presenting cells. The purpose of this study is to investigate the role of these retinal cells in antigen presentation in vivo and in the development of uveitis. Methods. (Lewis x Brown Norway)F1 [LBN/F1(RT-1l/n)] rats were made chimeric after lethal whole-body irradiation by transplanting 50x106 bone marrow cells from Brown Norway [BN(RT-1n)] donors. Three months after reconstitution, three rats of each groups; chimeric, Lewis [LEW(RT-11)], LBN/F1 and BN rats, were each given 15x106 S-antigen specific CD4+ LBN/F1 T cells by intracardiac injection. Highly purified CD4+ T cells were obtained and were confirmed by FACS analysis. MHC class II restriction was determined by a proliferation assay. All animals were sacrificed on the ninth day after adoptive transfer and the eyes were evaluated histologically. Results. All LEW and LBN/F1 rats showed typical features of EAU but none of chimeric rats developed the uveitis and BN rat eyes were normal. LBN/F1 CD4+ T cells were restricted only by LEW(RT-11). Conclusions. The failure of the chimeras to develop the uveitis with transfer of LEW-specific, MHC class II-restricted, uveitogenic T cells indicates that none of the retinal/uveal resident cells (with the exception of bone marrow derived cells) present S-antigen in the induction of EAU. Based on the present and previous studies it appears that bone marrow-derived cells are required for S-antigen presentation in vivo for the initiation of EAU.

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