CD45-mediated control of TCR tuning in naïve and memory CD8+ T cells

Abstract

Continuous contact with self-major histocompatibility complex (MHC) ligands is essential for survival of naïve T cells but not memory cells. This surprising finding implies that T cell subsets may vary in their relative T-cell receptor (TCR) sensitivity. Here we show that in CD8+T cells TCR sensitivity correlates inversely with levels of CD5, a marker for strong self-MHC reactivity. We also show that TCR sensitivity is lower in memory CD8+ T cells than naïve cells. In both situations, TCR hypo-responsiveness applies only to short-term TCR signalling events and not to proliferation, and correlates directly with increased expression of a phosphatase, CD45 and reciprocal decreased expression of activated LCK. Inhibition by high CD45 on CD8+ T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens.

Strong homeostatic TCR signals induce formation of self‐tolerant virtual memory CD8 T cells

“…Based on pilot studies in the field (Pihlgren et al , ; Curtsinger et al , ; London et al , ), it was generally accepted that one feature of immunological memory is that a memory T cell elicits a faster and stronger response to cognate antigens than a naïve T cell. However, recent evidence showed that, at least under certain conditions, the response of naïve T cells to an antigen is stronger than the response of memory T cells (Knudson et al , ; Mehlhop‐Williams & Bevan, ; Cho et al , ). We showed that true memory T cells surpass virtual memory T cells in the upregulation of KLRG1, CD25, and in their potency to induce experimental autoimmune pathology.…”

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

“…FoxP3 is a marker of regulatory T (Treg) cells which inhibit anti-tumor immune response [8]. CD45RO + T cells are known as memory T cells and have an auxiliary induction effect [9]. Therefore, the role of TILs in tumor-associated immune response is a kind of comprehensive effect regulated by the interaction of different subsets [10].…”

Regulation of autoimmune and anti‐tumour T‐cell responses by PTPN22

“…These data suggested that PTPN22 was important for the regulation of effector but not naïve T‐cell activation. Consistent with these findings, PTPN22 expression is elevated in effector and memory T‐cells relative to naïve T‐cells . More recently, studies using the OT‐I TCR transgenic mouse strain [that expresses an MHC class I restricted ovalbumin (ova)‐specific TCR] have shown that naïve T‐cell activation is regulated by PTPN22.…”

“…Consistent with these findings, PTPN22 expression is elevated in effector and memory T-cells relative to na€ ıve T-cells. 21,22 More recently, studies using the OT-I TCR transgenic mouse strain [that expresses an MHC class I restricted ovalbumin (ova)-specific TCR] have shown that na€ ıve T-cell activation is regulated by PTPN22. Thus, initial T-cell activation in response to high-affinity ova-peptide antigens was unaffected by loss of PTPN22 expression, consistent with previous data using cross-linking antibodies.…”