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CXCR5+CD8+ T cells are a distinct functional subset with an antitumor activity.


ABSTRACT: CXCR5 mediates homing of both B and follicular helper T (TFH) cells into follicles of secondary lymphoid organs. We found that CXCR5+CD8+ T cells are present in human tonsils and follicular lymphoma, inhibit TFH-mediated B cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5+CD8+ T cells into an animal model of lymphoma resulted in significantly greater antitumor activity than CXCR5-CD8+ T cells. Furthermore, RNA-Seq-based transcriptional profiling revealed 77 differentially expressed genes unique to CXCR5+CD8+ T cells. Among these, a signature comprised of 33 upregulated genes correlated with improved survival in follicular lymphoma patients. We also showed that CXCR5+CD8+ T cells could be induced and expanded ex vivo using IL-23 plus TGF-?, suggesting a possible strategy to generate these cells for clinical application. In summary, our study identified CXCR5+CD8+ T cells as a distinct T cell subset with ability to suppress TFH-mediated B cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.

SUBMITTER: Chu F 

PROVIDER: S-EPMC6814517 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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CXCR5 mediates homing of both B and follicular helper T (T<sub>FH</sub>) cells into follicles of secondary lymphoid organs. We found that CXCR5<sup>+</sup>CD8<sup>+</sup> T cells are present in human tonsils and follicular lymphoma, inhibit T<sub>FH</sub>-mediated B cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5<sup>+</sup>CD8<sup>+</sup> T cells into an animal model of lymphoma resulted in significantly greater antitumor a  ...[more]

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