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

• Published in: Blood Vol. 116; no. 25; pp. 5560 - 5570
• Main Authors: Wiehagen, Karla R., Corbo, Evann, Schmidt, Michelle, Shin, Haina, Wherry, E. John, Maltzman, Jonathan S.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 16.12.2010; Americain Society of Hematology; American Society of Hematology
• Series: Immunobiology
• Subjects: Adaptor Proteins, Signal Transducing - physiology; Animals; Biological and medical sciences; Blotting, Western; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation; Cell Proliferation; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Immunobiology; Immunologic Memory; Lymphocyte Activation; Lymphocytic Choriomeningitis - immunology; Lymphocytic Choriomeningitis - pathology; Lymphocytic Choriomeningitis - virology; Lymphocytic choriomeningitis virus - pathogenicity; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phosphoproteins - physiology; Receptors, Antigen, T-Cell - physiology; Signal Transduction; Persistence; Signal transduction; T cell receptor; Hematology; T-Lymphocyte; CD8 T lymphocyte; Memory lymphocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-06-292458

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.