SHP-1 in T cells limits the production of CD8 effector cells without impacting the formation of long-lived central memory cells

摘要

During responses against viruses and malignancies, naïve CD8 T lymphocytes expand to form both short-lived effector cells (SLECs) and a population containing cells with the potential to be long-lived and participate in memory responses (MPECs). The strength of antigenic, costimulatory, and cytokine signals during responses impacts the magnitude and type of CD8 populations formed. In vitro studies have revealed that the tyrosine phosphatase SHP-1 regulates signal transduction from receptors on T cells including the TCR, helping set the activation threshold, and therefore may shape responses of mature CD8 T cells in vivo. Analysis of CD8 T cells from motheaten mice, which are globally deficient in SHP-1, proved problematic due to cell-extrinsic effects of SHP-1 deficiency in non-T cells on CD8 T cells. Therefore, a conditional knockout of SHP-1 in mature single positive T cells was developed to analyze cell-intrinsic consequences of complete and partial SHP-1 deficiency on CD8 T cell responses to acute viral infection. The results demonstrated that SHP-1 has disparate effects on subpopulations of responding cells, limiting the magnitude and quality of primary and secondary responses by reducing the number of SLECs generated without affecting the size of the MPEC pool that leads to formation of long-term memory.