γδ T Cell Function Varies with the Expressed WC1 Coreceptor

WC1 molecules are transmembrane glycoproteins belonging to the scavenger receptor cysteine-rich family and uniquely expressed on γδ T cells. Although participation of WC1+ γδ T cells in immune responses is well established, very little is understood regarding the significance of expressing different forms of the WC1 molecule. Two forms previously identified by mAbs, i.e., WC1.1 and WC1.2, are expressed by largely nonoverlapping subpopulations of γδ T cells. In this study it was shown that expression of the WC1.1 coreceptor was the main indicator of proliferation and IFN-γ production in response to autologous and bacterial Ags as well as for IFN-γ production without proliferation in Th1-polarizing, IL-12-containing cultures. Nevertheless, after culture in either Th1-polarizing or neutral conditions, mRNA was present for both T-bet and GATA-3 as well as for IL-12Rβ2 in WC1.1+ and WC1.2+ subpopulations, and neither produced IL-4 under any conditions. Although the steady decrease in the proportion of WC1.1+ cells, but not WC1.2+ cells, within PBMC with animal aging suggested that the two subpopulations may have different roles in immune regulation, cells bearing either WC1.1 or WC1.2 expressed mRNA for regulatory cytokines IL-10 and TGF-β, with TGF-β being constitutively expressed by ex vivo cells. Overall, the results demonstrate that the form of the WC1 coreceptor expressed on γδ T cells divides them into functional subsets according to IFN-γ production and proliferative capacity to specific stimuli as well as with regard to representation within PBMC. Finally, evidence is provided for minor differences in the intracytoplasmic tail sequences of WC1.1 and WC1.2 that may affect signaling.