Background: In mice, natural killer (NK) T cells are specialized subsets of T cells that express an invariate T cell receptor (TCR) alpha chain and NK markers. In particular, murine NK1(+/-) T cells rapidly produce IL-4 and function as regulatory T cells.
Objective: We investigated the distribution of invariate TCR Valpha24JalphaQ T cells in CD4(-)CD8(-) double-negative (DN) and CD4(+) T cell populations of healthy individuals. We also studied the NK phenotypes and IL-4 production of Valpha24JalphaQ T cells.
Methods: The frequency of Valpha24(+/-) DN or CD4(+/-) T cells was determined by three-color FACS analysis, and subsequently the frequency of Valpha24JalphaQ rearrangement among Valpha24(+/-) DN or CD4(+/-) T cells was determined by sequencing.
Results: While the majority of DN Valpha24(+) T cells (68% to 88%) possessed TCR Valpha24JalphaQ, few of CD4(+) Valpha24(+) T cells (0.4% to 4%) did, indicating that Valpha24JalphaQ T cells are a major population of DN T cells, but not of CD4(+) T cells, in healthy subjects. The DN Valpha24JalphaQ T cells expressed a natural killer surface receptor NKR-P1A and CD56, but not CD16, on the cell surface. Moreover, DN Valpha24JalphaQ T cells promptly expressed IL-4 mRNA by stimulation with anti-Valpha24 monoclonal antibody in vitro.
Conclusion: From these phenotypic and functional similarities of human DN Valpha24JalphaQ T cells with murine NK1(+) Valpha14Jalpha281 T cells, we conclude that DN Valpha24JalphaQ T cells are a counterpart of murine NK1(+) T cells, suggesting that they may play a regulatory role in autoimmune responses in vivo.