Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection

Jacob V. Gorman, Gabriel Starbeck-Miller, Nhat Long L Pham, Geri L. Traver, Paul B. Rothman, John T. Harty, John D. Colgan

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

T cell Ig and mucin domain (Tim) 3 is a surface molecule expressed throughout the immune system that can mediate both stimulatory and inhibitory effects. Previous studies have provided evidence that Tim-3 functions to enforce CD8 T cell exhaustion, a dysfunctional state associated with chronic stimulation. In contrast, the role of Tim-3 in the regulation of CD8 T cell responses to acute and transient stimulation remains undefined. To address this knowledge gap, we examined how Tim-3 affects CD8 T cell responses to acute Listeria monocytogenes infection. Analysis of wild-type (WT) mice infected with L. monocytogenes revealed that Tim-3 was transiently expressed by activated CD8 T cells and was associated primarily with acquisition of an effector phenotype. Comparison of responses to L. monocytogenes by WT and Tim-3 knockout (KO) mice showed that the absence of Tim-3 significantly reduced the magnitudes of both primary and secondary CD8 T cell responses, which correlated with decreased IFN-γ production and degranulation by Tim-3 KO cells stimulated with peptide Ag ex vivo. To address the T cell-intrinsic role of Tim-3, we analyzed responses to L. monocytogenes infection by WT and Tim-3 KO TCR-transgenic CD8 T cells following adoptive transfer into a shared WT host. In this setting, the accumulation of CD8 T cells and the generation of cytokine-producing cells were significantly reduced by the lack of Tim-3, demonstrating that this molecule has a direct effect on CD8 T cell function. Combined, our results suggest that Tim-3 can mediate a stimulatory effect on CD8 T cell responses to an acute infection. The Journal of Immunology, 2014, 192: 3133-3142.

Original languageEnglish (US)
Pages (from-to)3133-3142
Number of pages10
JournalJournal of Immunology
Volume192
Issue number7
DOIs
StatePublished - Apr 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gorman, J. V., Starbeck-Miller, G., Pham, N. L. L., Traver, G. L., Rothman, P. B., Harty, J. T., & Colgan, J. D. (2014). Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection. Journal of Immunology, 192(7), 3133-3142. https://doi.org/10.4049/jimmunol.1302290