Independent regulation of lymphocytic choriomeningitis virus-specific T cell memory pools: Relative stability of CD4 memory under conditions of CD8 memory T cell loss

Infection of mice with a series of heterologous viruses causes a reduction of memory CD8(+) T cells specific to viruses from earlier infections, but t he fate of the virus-specific memory CD4(+) T cell pool following multiple virus infections has been unknown. We have previously reported that the vir us-specific CD4(+) Th precursor (Thp) frequency remains stable into long-te rm immunity following lymphocytic choriomeningitis virus (LCMV) infection. In this study, we questioned whether heterologous virus infections or injec tion with soluble protein CD4 Ags would impact this stable LCMV-specific CD 4(+) Thp memory pool. Limiting dilution analyses for IL-2-producing cells a nd intracellular cytokine staining for IFN-gamma revealed that the LCMV-spe cific CD4(+) Thp frequency remains relatively stable following multiple het erologous virus infections or protein Ag immunizations, even under conditio ns that dramatically reduce the LCMV-specific CD8+ CTL precursor frequency, These data indicate that the CD4(+) and CD8(+) memory T cell pools are reg ulated independently and that the loss in CD8(+) T cell memory following he terologous virus infections is not a consequence of a parallel loss in the memory CD4(+) T cell population.