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Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.


ABSTRACT: Concurrent helminth infection potently inhibits T cell immunity; however, whether helminthes prevent T cell priming or skew clonal recruitment and effector differentiation is not known. Using coinfection with two natural mouse pathogens, Heligmosomoides polygyrus and Toxoplasma gondii, to investigate the negative impact of helminthes on the CD8 T cell response, we demonstrate helminth-induced suppression of IL-12-dependent differentiation of killer-like receptor G1+ effector CD8 T cells and IFN-? production. Nevertheless, reversal of helminth suppression of the innate IL-12 response of CD8?+ dendritic cells, which occurred in STAT6-deficient mice, was not sufficient to normalize CD8 T cell differentiation. Instead, a combined deficiency in IL-4 and IL-10 was required to reverse the negative effects of helminth coinfection on the CD8 T cell response. Monoclonal T. gondii-specific CD8 T cells adoptively transferred into coinfected mice recapitulated the spectrum of helminth-induced effects on the polyclonal CD8 T response, indicating the lack of requirement for clonal skewing.

SUBMITTER: Marple A 

PROVIDER: S-EPMC5225035 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.

Marple Andrew A   Wu Wenhui W   Shah Suhagi S   Zhao Yanlin Y   Du Peicheng P   Gause William C WC   Yap George S GS  

Journal of immunology (Baltimore, Md. : 1950) 20161212 2


Concurrent helminth infection potently inhibits T cell immunity; however, whether helminthes prevent T cell priming or skew clonal recruitment and effector differentiation is not known. Using coinfection with two natural mouse pathogens, Heligmosomoides polygyrus and Toxoplasma gondii, to investigate the negative impact of helminthes on the CD8 T cell response, we demonstrate helminth-induced suppression of IL-12-dependent differentiation of killer-like receptor G1<sup>+</sup> effector CD8 T cel  ...[more]

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