CD27 Promotes Survival of Activated T Cells and Complements CD28 in Generation and Establishment of the Effector T Cell Pool

Abstract

CD27, like CD28, acts in concert with the T cell receptor to support T cell expansion. Using CD27−/− mice, we have shown earlier that CD27 determines the magnitude of primary and memory T cell responses to influenza virus. Here, we have examined the relative contributions of CD27 and CD28 to generation of the virus-specific effector T cell pool and its establishment at the site of infection (the lung), using CD27−/−, CD28−/−, and CD27/CD28−/− mice. We find that primary and memory CD8+ T cell responses to influenza virus are dependent on the collective contribution of both receptors. In the primary response, CD27 and CD28 impact to a similar extent on expansion of virus-specific T cells in draining lymph nodes. CD27 is the principle determinant for accumulation of virus-specific T cells in the lung because it can sustain this response in CD28−/− mice. Unlike CD28, CD27 does not affect cell cycle activity, but promotes survival of activated T cells throughout successive rounds of division at the site of priming and may do so at the site of infection as well. CD27 was found to rescue CD28−/− T cells from death at the onset of division, explaining its capacity to support a T cell response in absence of CD28.

CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression

“…In contrast to this, the provision of IL-2 signals to IL2Ra -/-T cells by an mAb/IL-2 complex during secondary response only moderately increased memory T cell expansion by approximately twofold [14]. In addition, CD27 signaling has been shown to contribute to CTL expansion even in the absence of IL-2 signaling, most likely by promoting survival of activated T cells by up-regulating anti-apoptotic proteins [26,40].…”

“…An important role of CD27-signaling on memory CTL has been documented after infection of CD27 -/-mice with influenza virus and LCMV [24,26,33]. CD27 has been shown to promote survival of activated T cells most likely by up-regulating anti-apoptotic proteins [26,38].…”

“…In addition, lymphocytic choriomeningitis virus (LCMV) immunization experiments with IL-2R-deficient T cells showed that induction and CD27 belongs to the tumor necrosis factor receptor (TNFR) family [22]. The interaction with its transmembrane ligand CD70, which is expressed on activated T and B cells and on subsets of dendritic cells and some NK cells, induces a costimulatory signal that activates NF-jB, promotes survival, enhances TCR-mediated expansion and increases effector function [23][24][25][26][27][28]. Because CD27 expression was lost after prolonged polyclonal stimulation in vitro, loss of CD27 was postulated as a marker for terminally differentiated memory T cells.…”

CD27 stimulation unveils the efficacy of linked class I/II peptide vaccines in poorly immunogenic tumors by orchestrating a coordinated CD4/CD8 T cell response

“…14–16 CD27, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory molecule expressed on naïve and activated CD4 + and CD8 + T cells 17 and is known to be important in T cell activation, 18 maturation, 19 cytokine secretion, 20 and survival, 21 making it a promising target for T cell-based immunomodulation. Recently, a novel, fully human anti-human CD27 monoclonal antibody (αhCD27) was developed which binds with high affinity to induce potent human T cell responses in the context of T cell receptor stimulation.…”

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

“…CD27, which is expressed on naive and long‐lived central memory T cells, complements CD28‐mediated T‐cell activation4 by counteracting apoptosis,5, 6, 7 promoting aerobic glycolysis7 and inducing expression of dendritic cell (DC) ‐targeting chemokines such as CXCL10 and XCL1 8. Furthermore, CD27 signalling promotes T helper type 1 responses9, 10 and is important, albeit not essential, for memory differentiation of CD8 T cells 11, 12, 13.…”