An Excess of the Proinflammatory Cytokines IFN-γ and IL-12 Impairs the Development of the Memory CD8+ T Cell Response to Chlamydia Trachomatis

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2015 Jul 17

PMID 26179901

Citations 11

Authors

Xuqing Zhang

Michael N Starnbach

Affiliations

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Abstract

The obligate intracellular bacterium Chlamydia trachomatis is the most common cause of bacterial sexually transmitted disease in the United States and the leading cause of preventable blindness worldwide. Transfer of cultured Chlamydia-specific CD8(+) T cells or vaccination with recombinant virus expressing an MHC I-restricted Chlamydia Ag confers protection, yet surprisingly a protective CD8(+) T cell response is not stimulated following natural infection. In this study, we demonstrate that the presence of excess IL-12 and IFN-γ contributes to poor memory CD8(+) T cell development during C. trachomatis infection of mice. IL-12 is required for CD8(+) T cell expansion but drives effector CD8(+) T cells into a short-lived fate, whereas IFN-γ signaling impairs the development of effector memory cells. We show that transient blockade of IL-12 and IFN-γ during priming promotes the development of memory precursor effector CD8(+) T cells and increases the number of memory T cells that participate in the recall protection against subsequent infection. Overall, this study identifies key factors shaping memory development of Chlamydia-specific CD8(+) T cells that will inform future vaccine development against this and other pathogens.

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