Collectively, our study suggests that the strength of the T cell response—influenced by the competition within the local environment and the location in the draining or non-draining secondary lymphoid organs—and the type of infection/antigen challenge seem to play a critical role in determining whether CXCR5– or CXCR5+ CD4+ T memory cells carry a central memory phenotype. This evidence concerns the gene CXCR5 and infection.