CD49d marks Th1 and Tfh-like antigen-specific CD4 + T cells during Plasmodium chabaudi infection.

Upon activation, specific CD4 + T cells upregulate the expression of CD11a and CD49d, surrogate markers of pathogen-specific CD4 + T cells. However, using TCR transgenic mice specific for a Plasmodium antigen, termed PbT-II, we found that activated CD4 + T cells develop not only to CD11a hiCD49d hi cells, but also to CD11a hiCD49d lo cells during acute Plasmodium infection. CD49d hi PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet, and produced IFN-γ, indicating that they were Th1-type cells. In contrast, CD49d lo PbT-II cells resided in the white pulp/marginal zones and were a heterogeneous population, with approximately half of them expressing CXCR5 and a third expressing Bcl-6, a master regulator of Tfh cells. In adoptive transfer experiments, both CD49d hi and CD49d lo PbT-II cells differentiated into CD49d hi Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49d hi and CD49d lo phenotypes were generally maintained in mice infected with P. chabaudi. These results suggest that CD49d is expressed on Th1-type Plasmodium-specific CD4 + T cells, which are localized in red pulp of the spleen, and can be used as a marker of antigen-specific Th1 CD4 + T cells, rather than that of all pathogen-specific CD4 + T cells.