Induction of a regulatory phenotype in human CD4(+) T cells by streptococcal M protein
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/211564
- author
- Price, JD ; Schaumburg, Jessica LU ; Sandin, Charlotta LU ; Atkinson, JP ; Lindahl, Gunnar LU and Kemper, C
- organization
- publishing date
- 2005
- 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
- 2016-04-01 16:10:54
- date last changed
- 2022-03-07 04:06:55
@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}},
url = {{http://www.jimmunol.org/cgi/reprint/175/2/677.pdf}},
volume = {{175}},
year = {{2005}},
}