Minimally activated CD8 autoreactive T cells specific for IRBP express a high level of Foxp3 and are functionally suppressive.
OBJECTIVE
Results in previous reports have demonstrated that immunization of the EAU-prone B6 mouse activates both CD4 and CD8 IRBP-specific T cells. The purpose of this study was to investigate structural and functional differences between CD4 and CD8 autoreactive T cells activated by the uveitogenic peptide.


METHODS
Purified CD4 and CD8 isolated from B6 mice immunized with an uveitogenic peptide, interphotoreceptor retinoid-binding protein (IRBP)1-20, were stimulated in vitro with various doses of immunizing peptide. The activated T cells were determined for cytokine production, expression of Foxp3, and suppressor activity.


RESULTS
CD4 autoreactive T cells underwent full activation when stimulated with high or medium concentrations of immunizing peptide, whereas a high dose of antigenic peptide resulted in only modest activation of CD8 autoreactive T cells. When stimulated by a low dose (<0.1 microg/mL) of antigen or by of a high dose of antigen and a small amount of TGF-beta1, the minimally activated CD8 T cells expressed a high level of Foxp3 and gained suppressor function.


CONCLUSIONS
Minimally activated CD8 autoreactive T cells can be functionally suppressive and may neutralize the tissue-damaging effect of the CD4 autoreactive T cells.
Peng
Yong
Y
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, USA.
Shao
Hui
H
Ke
Yan
Y
Zhang
Ping
P
Han
Gencheng
G
Kaplan
Henry J
HJ
Sun
Deming
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012177:Retinol-Binding Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015866:Uveitis, Posterior / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D016827:CD8 Antigens; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D007376:Interleukin-2; D012177:Retinol-Binding Proteins; D053773:Transforming Growth Factor beta1; D000099214:Retinol-Binding Proteins, Interstitial; C498833:Foxp3 protein, mouse