Homeostatic division is not necessary for antigen-specific CD4+ memory T cell persistence1

CD4 + memory T cells are generated in response to infection or vaccination, provide protection to the host against re-infection, and persist through a combination of enhanced survival and slow homeostatic turnover. We used timed deletion of the TCR-signaling adaptor molecule SH2-domain-containing phosphoprotein of 76 kDa (SLP-76) with MHC:peptide tetramers to study the requirements for tonic TCR signals in the maintenance of polyclonal antigen-specific CD4 + memory T cells. SLP-76 deficient I-A b :GP61 cells are unable to rapidly generate effector cytokine or proliferate in response to secondary infection. In mice infected with lymphocytic choriomeningitis virus (LCMV) or Listeria monocytogenes expressing the LCMV GP61-80 peptide, SLP-76 deficient I-A b :GP61 + cells exhibit reduced division, similar to that seen in in vitro generated CD44 hi and endogenous CD4 + CD44 hi cells. Competitive bone marrow chimera experiments demonstrated that the decrease in homeostatic turnover in the absence of SLP-76 is a cell intrinsic process. Surprisingly, despite the reduction in turnover, I-A b :GP61 + antigen-specific memory cells persist in normal numbers for more than 30 weeks post LCMV infection in the absence of SLP-76. These data suggest the independent maintenance of a population of antigen-specific CD4 + memory T cells in the absence of SLP-76 and normal levels of homeostatic division.