Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b

Shuning Zhang, Mike Rozell, Raj K. Verma, Diana I. Albu, Danielle Califano, Jeffrey Van Valkenburgh, Akeel Merchant, Javier Rangel-Moreno, Troy D. Randall, Nancy A. Jenkins, Neal G. Copeland, Pentao Liu, Dorina Avram

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1 hiCD127lo effector CD8+ T cells were formed during the course of infection in the absence of Bcl11b, albeit in smaller numbers, and their Ag-specific cytolytic activity on a per-cell basis was altered, which was associated with reduced granzyme B and perforin.

Original languageEnglish (US)
Pages (from-to)1687-1699
Number of pages13
JournalJournal of Experimental Medicine
Volume207
Issue number8
DOIs
StatePublished - Aug 2 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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