The low CTLA-4 and LIR-1 expression by CD4+IFN-γ-producing T cells specific for a cleared protein vaccine as tetanus/diphtheria, in contrast to the high CTLA-4 and or LIR-1 expression by T. cruzi antigen-responsive CD4+ T cells, supports the conclusion that chronic antigen stimulation with T. cruzi drives CTLA-4 and LIR-1 expression on T cells. The gene discussed is CD4; the disease is diphtheria.