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

Jeffrey D. Price, Jessica Schaumburg, Charlotta Sandin, John P. Atkinson, Gunnar Lindahl*, Claudia Kemper

*Korrespondierende/r Autor/-in für diese Arbeit
59 Zitate (Scopus)


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 MS and M22 proteins were found to induce T cells to develop into the IL-10-producing Tr1-like phenotype. Moreover, whole MS-expressing bacteria, but not isogenic M-negative bacteria, led to proliferation and IL-10 secretion by T cells. The interaction between the MS protein and T cells was dependent on CD46 and the conserved C repeat region of MS. 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.

ZeitschriftJournal of Immunology
Seiten (von - bis)677-684
PublikationsstatusVeröffentlicht - 15.07.2005

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)


Untersuchen Sie die Forschungsthemen von „Induction of a regulatory phenotype in human CD4+ T cells by streptococcal M protein“. Zusammen bilden sie einen einzigartigen Fingerprint.