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

Price, JD; Schaumburg, Jessica LU ; Sandin, Charlotta LU ; Atkinson, JP; Lindahl, Gunnar LU and Kemper, C (2005) In Journal of Immunology 175(2). p.677-684
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
175
issue
2
pages
677 - 684
publisher
American Association of Immunologists
external identifiers
  • wos:000233647600006
  • pmid:16002662
  • scopus:23244448609
ISSN
1550-6606
language
English
LU publication?
yes
id
83f3ecaf-bd8a-48b8-9a8d-cb1e560c6b81 (old id 211564)
alternative location
http://www.jimmunol.org/cgi/reprint/175/2/677.pdf
date added to LUP
2007-08-15 14:37:59
date last changed
2017-04-09 04:18:02
@article{83f3ecaf-bd8a-48b8-9a8d-cb1e560c6b81,
  abstract     = {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.},
  author       = {Price, JD and Schaumburg, Jessica and Sandin, Charlotta and Atkinson, JP and Lindahl, Gunnar and Kemper, C},
  issn         = {1550-6606},
  language     = {eng},
  number       = {2},
  pages        = {677--684},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Induction of a regulatory phenotype in human CD4(+) T cells by streptococcal M protein},
  volume       = {175},
  year         = {2005},
}