Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration

M Kurachi, J Kurachi, F Suenaga, T Tsukui… - Journal of experimental …, 2011 - rupress.org
M Kurachi, J Kurachi, F Suenaga, T Tsukui, J Abe, S Ueha, M Tomura, K Sugihara
Journal of experimental medicine, 2011rupress.org
Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the
effector versus memory cell fate decision of CD8+ T cells. But it is not known how early
lymphocyte distribution after infection has an impact on this process. We demonstrate that
the chemokine receptor CXCR3 is involved in promoting CD8+ T cell commitment to an
effector fate rather than a memory fate by regulating T cell recruitment to an
antigen/inflammation site. After systemic viral or bacterial infection, the contraction of …
Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the effector versus memory cell fate decision of CD8+ T cells. But it is not known how early lymphocyte distribution after infection has an impact on this process. We demonstrate that the chemokine receptor CXCR3 is involved in promoting CD8+ T cell commitment to an effector fate rather than a memory fate by regulating T cell recruitment to an antigen/inflammation site. After systemic viral or bacterial infection, the contraction of CXCR3−/− antigen-specific CD8+ T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8+ T cells. Early after infection, CXCR3−/− antigen-specific CD8+ T cells fail to cluster at the marginal zone in the spleen where inflammatory cytokines such as IL-12 and IFN-α are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3−/− CD8+ T cells exhibit transient expression of CD25 and preferentially differentiate into memory precursor effector cells as compared with wild-type CD8+ T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8+ T cells via inhibition of CXCR3-mediated T cell migration to inflamed microenvironments.
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