In contrast, previous studies using infections with viruses [10,26] and bacteria [8,11,12] showed that an absence of ICOS costimulatory signaling activity, induced by either the genetic deletion of ICOS or the blocking of its functions by anti-ICOS mAbs or ICOS-Ig (a fusion protein of ICOS and the Fc region of human IgG1), downregulates [8,10,11,12] or does not affect [26] the cytotoxic activity and/or IFN-γ production of CD8+ T cells during those microbial infections. This evidence concerns the gene CD8A and infection.