The effects of p16^INK4a deletion on age-related changes in homeostatic or antigen-specific proliferation of memory and naive T cells. (A) Representative flow analyses of in vivo proliferation as measured by BrdU incorporation in memory or naive T cells without NP immunization (homeostatic, −) or with NP immunization (antigen-specific, +) in mice of indicated ages and genotypes. For NP(+) results, BrdU incorporation in memory or naive T cells is determined after reimmunization with nitrophenylacetyl-chicken γ-globulin as described in “Immune function is enhanced in old mice by T-lineage deletion of p16^INK4a.” (B) Quantification of BrdU incorporation in memory (bottom) or naive (top) as shown in panel A with and without NP immunization; n = 4-5 mice per group. T cell–specific inactivation of p16^INK4a is associated with rescue of an age-associated decline in antigen-specific proliferation in memory and naive T cells and homeostatic proliferation in memory cells. Memory and naive T cells are identified as described in Figure 1C. (C) Representative flow analyses in 100-week-old mice of indicated genotypes showing the effect of T lineage–specific p16^INK4a deletion on T-cell helper function as measured by antigen-induced B-cell proliferation (BrdU incorporation). (D) Quantification of antigen-induced B-cell proliferation as measured in panel C; n = 4 mice per group. Error bars indicate SEM; *P < .05, **P < .01, ***P < .001.