Population doublings of murine CD4⁺ memory T cells during continuous antigen stimulation in vivo

We investigated the expansion rate of CD4⁺ memory T cells using a newly developed in vivo system. Neonatal thymectomy abrogates the subsequent production of T cells and induces autoimmune gastritis (AIG) by the activation of CD4⁺ T cells; this disease was transferred into athymic nude mice through the inoculation of splenic CD4⁺ memory T cells. The transferred CD4⁺ T cells increased logarithmically in number during the first 2months in the spleen of the recipients. The serial transfer of these splenocytes at two-month intervals revealed that the numbers of the AIG-transferable generations were inversely correlated with the age of the first AIG donors. The duration of the AIG-promoting capacity of CD4⁺ T cells under continuous antigenic stimulation in vivo was approximately equivalent-one and a half years. These results indicate that there exists an intrinsic population doubling limit in memory CD4⁺ T cells similar to that of self-renewing naïve ones.