Interestingly, low dose x31 (H3N2) immunization did not induce GrB expressing CD4 effectors at the primary response, but did generate high numbers of CD4 CTL in the secondary response (45), again suggesting that the inflammatory microenvironment in the lung may provide second signals for complete differentiation of CD4 CTL, as x31 infection does not promote as high of an inflammatory response compared to CpG (45) or PR8 (40). This evidence concerns the gene CD4 and infection.