Major role of gamma delta T cells in the generation of IL-17+ uveitogenic T cells.
We show that in vitro activation of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from C57BL/6 mice immunized with an uveitogenic IRBP peptide (IRBP(1-20)) under TH17-polarizing conditions is associated with increased expansion of T cells expressing the gammadelta TCR. We also show that highly purified alphabeta or gammadelta T cells from C57BL/6 mice immunized with IRBP(1-20) produced only small amounts of IL-17 after exposure to the immunizing Ag in vitro, whereas a mixture of the same T cells produced greatly increased amounts of IL-17. IRBP-induced T cells from IRBP-immunized TCR-delta(-/-) mice on the C57BL/6 genetic background produced significantly lower amounts of IL-17 than did wild-type C57BL/6 mice and had significantly decreased experimental autoimmune uveitis-inducing ability. However, reconstitution of the TCR-delta(-/-) mice before immunization with a small number of gammadelta T cells from IRBP-immunized C57BL/6 mice restored the disease-inducing capability of their IRBP-specific T cells and greatly enhanced the generation of IL-17(+) T cells in the recipient mice. Our study suggests that gammadelta T cells are important in the generation and activation of IL-17-producing autoreactive T cells and play a major role in the pathogenesis of experimental autoimmune uveitis.
Cui
Yan
Y
Doheny Eye Institute, Department of Ophthalmology, University of Southern California, 90033, USA.
Shao
Hui
H
Lan
Chen
C
Nian
Hong
H
O'Brien
Rebecca L
RL
Born
Willi K
WK
Kaplan
Henry J
HJ
Sun
Deming
D
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005136:Eye Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014605:Uveitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D018984:Epitopes, T-Lymphocyte; D005136:Eye Proteins; D020381:Interleukin-17; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial