CD4 and infection: In the Trypanosoma cruzi (T. cruzi) infection-induced CD4+ T cell unresponsiveness model, infection with T. cruzi led to a significant increase in the expression of both CTLA-4 and PD-1 in spleen CD4+ T cells, which might be attributed to the upregulation of the E3 ubiquitin ligase GRAIL (gene related to anergy in lymphocytes) during infection.