Abstract
SummaryTo gain insights into the molecular mechanisms and pathways involved in the activation of γ-herpesvirus (MHV68)-specific T cell receptor transnuclear (TN) CD8+ T cells, we performed a comprehensive transcriptomic analysis. Upon viral infection, we observed differential expression of several thousand transcripts encompassing various networks and pathways in activated TN cells compared with their naive counterparts. Activated cells highly upregulated galectin-3. We therefore explored the role of galectin-3 in influencing anti-MHV68 immunity. Galectin-3 was recruited at the immunological synapse during activation of CD8+ T cells and helped constrain their activation. The localization of galectin-3 to immune synapse was evident during the activation of both naive and memory CD8+ T cells. Galectin-3 knockout mice mounted a stronger MHV68-specific CD8+ T cell response to the majority of viral epitopes and led to better viral control. Targeting intracellular galectin-3 in CD8+ T cells may therefore serve to enhance response to efficiently control infections.
Highlights
Induction of an adaptive immune response and the formation of effective immunological memory are essential for protective immunity against infectious diseases (Ahmed and Gray, 1996)
We generated murine herpesvirus 68 (MHV68)-specific CD8+ T cell receptor transnuclear (TCR TN) mice by somatic cell nuclear transfer approach to investigate the contribution of CD8+ T cells to viral control (Sehrawat et al, 2012)
We demonstrate that galectin-3 is recruited at the immunological synapse but predominantly acts intracellularly within CD8+ T cells engaged to cognate peptide displayed by major histocompatibility complex (MHC) I both during the primary and memory response
Summary
Induction of an adaptive immune response and the formation of effective immunological memory are essential for protective immunity against infectious diseases (Ahmed and Gray, 1996). Pathogen-specific CD8+ T cell responses are usually polyclonal in nature and recognize multiple epitopes specified by the invading pathogen (Wong and Pamer, 2003). This applies in particular to complex pathogens such as poxviruses and herpesviruses (HVs) in their natural hosts (Amanna et al, 2006; Freeman et al, 2010; Gredmark-Russ et al, 2008; Moutaftsi et al, 2006). We generated MHV68-specific CD8+ T cell receptor transnuclear (TCR TN) mice by somatic cell nuclear transfer approach to investigate the contribution of CD8+ T cells to viral control (Sehrawat et al, 2012). CD8+ TCR TN mice are likely to yield physiologically relevant primary T cell populations to investigate their responsiveness during infection (Kirak et al, 2010; Sehrawat et al, 2012)
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