Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8⁺ memory T cells

The requirements for tonic T-cell receptor (TCR) signaling in CD8 ⁺ memory T-cell generation and homeostasis are poorly defined. The SRC homology 2 (SH2)-domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for proximal TCR-generated signaling.We used temporally mediated deletion of SLP-76 to interrupt tonic and activating TCR signals after clearance of the lymphocytic choriomeningitis virus (LCMV). SLP-76-dependent signals are required during the contraction phase of the immune response for the normal generation of CD8 memory precursor cells. Conversely, LCMV-specific memory CD8 T cells generated in the presence of SLP-76 and then acutely deprived of TCR-mediated signals persist in vivo in normal numbers for more than 40 weeks. Tonic TCR signals are not required for the transition of the memory pool toward a central memory phenotype, but the absence of SLP-76 during memory homeostasis substantially alters the kinetics. Our data are consistent with a model in which tonic TCR signals are required at multiple stages of differentiation, but are dispensable for memory CD8 T-cell persistence.