The Pim Kinase Pathway Contributes to Survival Signaling in Primed CD8+ T Cells upon CD27 Costimulation
Open Access
- 1 December 2010
- journal article
- Published by The American Association of Immunologists
- Vol. 185 (11), 6670-6678
- https://doi.org/10.4049/jimmunol.1000159
Abstract
Stimulation of the costimulatory receptor CD27 by its ligand CD70 has proved important for the generation of primary and memory CD8+ T cell responses in various models of antigenic challenge. CD27/CD70-mediated costimulation promotes the survival of primed T cells and thereby increases the size of effector and memory populations. In this paper, we reveal molecular mechanisms underlying the prosurvival effect of CD27. CD27 signaling upregulated expression of the antiapoptotic Bcl-2 family member Bcl-xL. However, genetic reconstitution of Cd27−/− CD8+ T cells with Bcl-xL alone or in combination with the related protein Mcl-1 did not compensate for CD27 deficiency in the response to influenza virus infection. This suggested that CD27 supports generation of the CD8+ effector T cell pool not only by counteracting apoptosis via Bcl-2 family members. Genome-wide mRNA expression profiling indicated that CD27 directs expression of the Pim1 gene. Pim-1 is a serine/threonine kinase that sustains survival of rapidly proliferating cells by antiapoptotic and prometabolic effects that are independent of the mammalian target of rapamycin (mTOR) pathway. In TCR-primed CD8+ T cells, CD27 could increment Pim-1 protein expression and promote cell survival throughout clonal expansion independent of the mTOR and IL-2R pathways. In addition, introduction of the Pim1 gene in Cd27−/− CD8+ T cells partially corrected their defect in clonal expansion and formation of an effector pool. We conclude that CD27 may contribute to the survival of primed CD8+ T cells by the upregulation of antiapoptotic Bcl-2 family members but also calls the Pim-1 kinase survival pathway into action.Keywords
This publication has 53 references indexed in Scilit:
- Expression of Costimulatory Ligand CD70 on Steady-State Dendritic Cells Breaks CD8+ T Cell Tolerance and Permits Effective ImmunityImmunity, 2008
- During Viral Infection of the Respiratory Tract, CD27, 4-1BB, and OX40 Collectively Determine Formation of CD8+ Memory T Cells and Their Capacity for Secondary ExpansionPublished by The American Association of Immunologists ,2005
- CD27 and CD70 in T cell and B cell activationCurrent Opinion in Immunology, 2005
- TNF/TNFR FAMILY MEMBERS IN COSTIMULATION OF T CELL RESPONSESAnnual Review of Immunology, 2005
- CD70 Signaling Is Critical for CD28-Independent CD8+ T Cell-Mediated Alloimmune Responses In VivoPublished by The American Association of Immunologists ,2005
- Induction of CD70 on Dendritic Cells through CD40 or TLR Stimulation Contributes to the Development of CD8+ T Cell Responses in the Absence of CD4+ T CellsThe Journal of Immunology, 2005
- Tumor Rejection Induced by CD70-mediated Quantitative and Qualitative Effects on Effector CD8+ T Cell FormationThe Journal of Experimental Medicine, 2004
- CD27 Promotes Survival of Activated T Cells and Complements CD28 in Generation and Establishment of the Effector T Cell PoolThe Journal of Experimental Medicine, 2003
- Expression of the Murine CD27 Ligand CD70 In Vitro and In VivoPublished by The American Association of Immunologists ,2003
- Population Biology of Lymphocytes: The Flight for SurvivalAnnual Review of Immunology, 2000