CD27-CD70 Costimulation Controls T Cell Immunity during Acute and Persistent Cytomegalovirus Infection

Abstract

f Cytomegaloviruses (CMVs) establish lifelong infections that are controlled in part by CD4؉ and CD8 ؉ T cells. To promote persistence, CMVs utilize multiple strategies to evade host immunity, including modulation of costimulatory molecules on infected antigen-presenting cells. In humans, CMV-specific memory T cells are characterized by the loss of CD27 expression, which suggests a critical role of the costimulatory receptor-ligand pair CD27-CD70 for the development of CMV-specific T cell immunity. In this study, the in vivo role of CD27-CD70 costimulation during mouse CMV infection was examined. During the acute phase of infection, the magnitudes of CMV-specific CD4؉ and CD8 ؉ T cell responses were decreased in mice with abrogated CD27-CD70 costimulation. Moreover, the accumulation of inflationary memory T cells during the persistent phase of infection and the ability to undergo secondary expansion required CD27-CD70 interactions. The downmodulation of CD27 expression, however, which occurs gradually and exclusively on inflationary memory T cells, is ligand independent. Furthermore, the IL-2 production in both noninflationary and inflationary CMV-specific T cells was dependent on CD27-CD70 costimulation. Collectively, these results highlight the importance of the CD27-CD70 costimulation pathway for the development of CMV-specific T cell immunity during acute and persistent infection.

The activation of the adaptive immune system: Cross-talk between antigen-presenting cells, T cells and B cells

“…Whereas CD28-mediated costimulation most profoundly influences the expansion of MCMV-specific Tcm [112], the TNFR family members 4-1BB and OX40 are more important for the inflating Tem [113,114]. Interactions between the TNFR family member CD27 expressed on T cells and its ligand CD70 were found to be significant for both [115]. The work by Borst, van Lier and colleagues clearly demonstrated that CD27-CD70 interactions control also many other important aspects of T cell activation and differentiation, and tight regulation of this costimulatory receptor-ligand pair is required to avoid detrimental consequences [116][117][118][119][120][121][122][123].…”

Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity

“…To identify the molecular interactions that provide the help signal, we specifically focused on the role of costimulatory pathways involving the Ig superfamily member CD28 and its ligands B7.1 (CD80) and B7.2 (CD86) (here referred as B7) and the TNFR family member CD27 and its ligand CD70, because Cd80/86 Ϫ/Ϫ and Cd70 Ϫ/Ϫ mice have reduced MCMV-specific CD4 ϩ T cell responses ( Fig. 3B) (18,24). No differences were found in the MCMV-specific IgM response during acute and persistent infection in all mice devoid of B7-and/or CD70-mediated costimulatory signals (Fig.…”

“…Erythrocytes were lysed in a hypotonic ammonium chloride buffer. The antigen-specific T cell response was determined by MHC class I tetramers and intracellular cytokine staining as described previously (18 24 -38 [20])-restricted peptides. Fluorescently conjugated antibodies were purchased by Affymetrix, BD Pharmingen, or BioLegend.…”

CD27-Mediated Regulatory T Cell Depletion and Effector T Cell Costimulation Both Contribute to Antitumor Efficacy

“…CD27 signaling is controlled by its ligand, CD70, the expression of which is transient upon activation of dendritic cells (DCs), B cells, and T cells, and is tightly regulated (11)(12)(13). CD70-CD27 interaction provides a potent second signal for CD4 T cell-dependent and -independent CD8 T cell priming, effector differentiation, and memory development in virus clearance or tumor rejection (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Human CD27 or CD70 deficiency due to genetic mutations resulted in persistent symptomatic EBV infection and EBV-associated lymphoproliferative disorders, including lethal lymphoma (26)(27)(28)(29)(30).…”