CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

Trivikram Dasu, Joseph E. Qualls, Halide Tuna, Chander Raman, Donald A. Cohen, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

A subset of CD4+ T cells, the CD4+ CD25+ regulatory T (Treg) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such 'natural regulatory (Treg) cells' and for activation of the effector function of CD4+ CD25+ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, tonsils and spleen. CD5 acts as a negative regulator of T cell and B cell signaling via recruitment of SHP-1. Here, we demonstrate that Treg cells obtained from CD5-/- mice are more potent than those from wild type mice in suppressing the in vitro cell proliferation of anti-CD3 stimulated CD4+ CD25- responder T cells. This phenomenon was cell contact and GITR dependent. Lack of CD5 expression on Treg cells (from spleen, lymph node and thymus) did not affect the intracellular levels of Foxp3. However, CD5-/- Treg thymocytes were able to elicit a higher Ca2+ response to TCR + co-stimulatory signals than the wild type cells. CD5-/- mice expressed more Foxp3 mRNA in the colon than wild type mice, and additionally, the severity of the dextran sulfate sodium (DSS)-induced colitis in CD5-/- mice was less than the wild type strain. We suggest that manipulation of CD5 expression or the downstream signaling components of CD4+ CD25+ Treg cells as a potential strategy for therapeutic intervention in cases of auto-immune disorders.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalImmunology Letters
Volume119
Issue number1-2
DOIs
StatePublished - Aug 15 2008

Bibliographical note

Funding Information:
This research has been supported by NIH grants to SB and CR. We thank Mr. Darrell Robertson for his expert technical assistance and Ms. Jennifer Strange and Greg Bowman for their assistance with flow cytometry.

Keywords

  • CD5
  • DSS-colitis
  • Murine CD4 CD25 T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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