In vivo reduction of telomere length in human antigen-reactive memory T cells

There is a reduction in the average telomere lengths of CD4(+) "memory" T c ells, defined by the CD45RO(+) phenotype, compared to CD54RA(+) "naive" T c ells. However, other studies suggest that telomerase activity often is suff icient to maintain the telomere length of certain B and T cell populations following immune activation in vivo. Thus it is uncertain whether genuine m emory CD4(+) T cells, defined by an immune response to specific recall anti gens, would display telomeres of reduced length, or whether telomere size w ould be maintained. Therefore, we examined the telomere lengths of T cells responding to two common recall antigens, tetanus toroid and Candida albica ns. Telomere terminal restriction fragment length was assessed by Southern blots or by flow cytometry following in situ hybridization with telomere-sp ecific peptide nucleic acid probes. For the five subjects tested, the Candi da- or tetanus-reactive memory T cell populations demonstrated a significan t reduction of telomere length even when compared to the phenotypically def ined memory CD45RO(+) T cell populations isolated from peripheral blood mon onuclear cells. This finding suggests that telomerase activity does not ful ly compensate for the effects of in vivo activation and proliferation of so me antigen-specific CD4(+) T cell populations. This may contribute to immun e senescence.