Proliferative and Regenerative Capacities of CD4+ T Cells upon TCR Stimulation

Proliferation of activated CD4+ T cells effectively amplifies the immune response. Based on a model of selective CD4+ T cell proliferation using an anti-CD3:anti-CD8 bispecific monoclonal antibody that leads to selective proliferation of CD4+ T cells, we demonstrated that the peripheral CD4+ T cells of normal subjects can divide for 17 to 38 generations, expanding 1.7 × 105 to 3 × 1011 fold, following a single short period of anti-TCR stimulation. The proliferating CD4+ T cells maintained IL2R expression. A large subgroup from each subject maintained the CD45RAhiCD45ROlo phenotype, demonstrating that activation and proliferation do not automatically convert CD4+ T cells into CD45RAloCD45ROhi phenotype. The enormous number of cells generated demonstrated that the peripheral CD4+ T cells have remarkable regenerative expansion capacity. The high, but substantially variable, proliferative capacities among subjects have important implications for diseases in which CD4+ T cells play an important role, such as HIV-infection, graft rejection, and autoimmunity.