Signaling through the T1/ST2 Molecule Is Not Necessary for Th2 Differentiation but Is Important for the Regulation of Type 1 Responses in NonhealingLeishmaniamajorInfection

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Abstract
T1/ST2 is a stable cell surface marker selectively expressed on type 2 T helper (Th2) effector cells. Since nonhealingLeishmaniamajorinfections in susceptible BALB/c mice have been ascribed to a polarized Th2 response, we used an anti-T1/ST2 monoclonal antibody (MAb) or a T1-Fc fusion protein to investigate the role of CD4+T1/ST2+Th2 cells in experimental leishmaniasis. We show that interfering with T1/ST2 signaling had no effect on lesion development or parasite replication; however, it induced a significantly higher type 1 response and an enhanced capacity of CD4+T cells to respond to interleukin 12 (IL-12). Surprisingly, even in the presence of an elevated Th1 response, the production of antigen-specific type 2 cytokines was not altered in the group of mice treated with the anti-T1/ST2 MAb or the T1-Fc fusion protein. To characterize further this Th2 response, we assessed the cytokine profile of CD4+T cells and found that interfering with T1/ST2 signaling did not alter the cytokine profile of CD4+T1/ST2+T cells. These results show that T1/ST2 signaling is not necessary for the differentiation of naive CD4+T cells into antigen-specific CD4+T1/ST2+Th2 cells. In addition to CD4+T1/ST2+T cells, we detected another subpopulation of CD4+Th2 cells, negative for the expression of T1/ST2, that could differentiate in vivo in response toL.majorinfection. Taken together, our results suggest that CD4+T1/ST2+Th2 cells but not CD4+T1/ST2−Th2 cells can downregulate the Th1 response during the course of a nonhealingL.majorinfection through a mechanism that is independent of IL-4 or IL-10.