In vitro activation of CD8 interphotoreceptor retinoid-binding protein-specific T cells requires not only antigenic stimulation but also exogenous growth factors.
In a previous study, we demonstrated that immunization with the uveitogenic peptide interphotoreceptor retinoid-binding protein (IRBP) 1-20 induces both CD4 and CD8 uveitogenic T cells in the B6 mouse. In the current study, we determined the role of the CD8 IRBP-specific T cells in the pathogenesis of experimental autoimmune uveitis. We also determined the conditions that facilitated the activation of CD8 autoreactive T cells. Our results showed that the beta2-microglobulin(-/-) mouse had a greatly decreased susceptibility to induction of experimental autoimmune uveitis by adoptive transfer of IRBP-specific T cells from B6 mice. We also showed that unlike CD4 autoreactive T cells, activated CD8 autoreactive T cells produced only a limited number and amounts of growth factors. As a result, in the absence of exogenously supplied growth factor(s), CD8 T cell activation and expansion were aborted. However, the growth and expansion of triggered CD8 autoreactive T cells could be supported by various cytokines. In addition to factors produced by activated CD4 autoreactive T cells, factors produced by nonlymphoid cells, such as IL-7 and IL-15, and unidentified factors in the culture supernatants of astrocytes and retinal pigment epithelial cells support the CD8 autoreactive T cells as well. Finally, we showed that, although several cytokines augmented the CD8 T cell response in vitro, different cytokines appeared to act on different CD8 subsets or on different activation/differentiation phases of CD8 autoreactive T cells. As a result, cytokines, such as IL-7, supported the proliferation and survival of CD8 IRBP-specific T cells, while others had only a growth-promoting effect.
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Yong
Y
Peng
Hui
H
Shao
Yan
Y
Ke
Ping
P
Zhang
Jim
J
Xiang
Henry J
HJ
Kaplan
Deming
D
Sun
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000008:administration & dosage; D004357:Drug Synergism; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012177:Retinol-Binding Proteins / Q000276:immunology*; D014605:Uveitis / Q000209:etiology / Q000276:immunology; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial