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Induction of a regulatory phenotype in human CD4(+) T cells by streptococcal M protein

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Author

  • JD Price
  • Jessica Schaumburg
  • Charlotta Sandin
  • JP Atkinson
  • Gunnar Lindahl
  • C Kemper

Summary, in English

Regulatory T cells (Tregs) participate in the control of the immune response. In the human system, an IL-10-secreting, T regulatory type 1 cell (Tr1)-like subset of Tregs can be induced by concurrent cross-linking of the TCR and CD46 on naive CD4(+) T cells. Because many viral and bacterial pathogens, including the major human pathogen Streptococcus pyogenes, bind to CD46, we asked whether this bacterium can directly induce Tr1-like cells through the streptococcal ligand for CD46, the M protein. The M5 and M22 proteins were found to induce T cells to develop into the IL-10-producing Tr1-like phenotype. Moreover, whole M5-expressing bacteria, but not isogenic M-negative bacteria, led to proliferation and IL-10 secretion by T cells. The interaction between the M5 protein and T cells was dependent on CD46 and the conserved C repeat region of M5. Supernatants derived from T cells stimulated with M proteins or M protein-expressing bacteria suppressed bystander T cell proliferation through IL-10 secretion. In addition, activation of CD46 through streptococcal M protein induced the expression of granzyme B, providing a second means for these cells to regulate an immune response. These findings suggest that binding to CD46 and exploiting its signaling pathway may represent a strategy employed by a number of important human pathogens to induce directly an immunosuppressive/regulatory phenotype in T cells.

Publishing year

2005

Language

English

Pages

677-684

Publication/Series

Journal of Immunology

Volume

175

Issue

2

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Immunology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1550-6606