Regulatory effect of gammadelta T cells on IL-17+ uveitogenic T cells.
OBJECTIVE
To characterize the regulatory effect of gammadelta T cells in the activation of IL-17+ uveitogenic T cells.


METHODS
The authors administered the gammadelta TCR-specific antibody GL3 to B6 mice before or after antigen immunization and examined Th1- or Th17-polarized T-cell responses. The intensity of Th17 responses was also examined in responder T cells containing varying numbers of gammadelta T cells.


RESULTS
GL3 treatment resulted in varying degrees of depletion of circulating gammadelta T cells, depending on when the antibody was administered. The intensity of the alphabetaTCR+IL-17+, but not the alphabetaTCR+IFN-gamma+, IRBP-specific T-cell responses was correlated to the percentage of gammadelta T cells in the responder T cells. Kinetic studies showed that early IL-17+ T cells were primarily gammadelta T cells, with a later gradual shift to alphabeta T cells. A close association was seen between the intensity of the IL-17+ autoreactive T-cell response and the percentage of gammadelta T cells in the responder T cells. Although a modest increase in gammadelta T cells among the responder T cells promoted the expansion of IL-17+ alphabetaTCR+ T cells, a higher proportion of gammadelta T cells inhibited it.


CONCLUSIONS
gammadelta T cells are actively involved in the generation of alphabetaTCR+IL-17+ T cells. The number of gammadelta T cells and the alphabeta/gammadelta T-cell ratio in the responder T cells regulate the intensity of the Th17-type autoreactive T-cell response.
Nian
Hong
H
Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, California 90033, USA.
Shao
Hui
H
Zhang
Guoming
G
Born
Willi K
WK
O'Brien
Rebecca L
RL
Kaplan
Henry J
HJ
Sun
Deming
D
D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology; D001324:Autoantigens / Q000494:pharmacology; D015551:Autoimmunity / Q000276:immunology; D005260:Female; D007114:Immunization; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014602:Uvea / Q000166:cytology / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta