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

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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

61 Citeringar (SciVal)

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)677-684
TidskriftJournal of Immunology
Volym175
Utgåva2
StatusPublished - 2005

Ämnesklassifikation (UKÄ)

  • Immunologi inom det medicinska området

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