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TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation.
Eur J Immunol 2005; 35(10):2886-95EJ

Abstract

Naturally occurring CD4+ CD25+ regulatory T cells (Treg) are potent suppressors of CD4+ and CD8+ T cell responses in vitro and inhibit several organ-specific autoimmune diseases. While most in vitro studies suggest that CD4+ CD25+ Treg cells adopt a cytokine-independent but cell contact-dependent mode of T cell regulation, their precise mechanism of suppression in vivo remains largely unknown. Here we examine the functional contribution of Treg cell-derived TGF-beta1 and effector T cell responsiveness to TGF-beta in CD4+ CD25+ T cell-mediated suppression of inflammatory bowel disease (IBD). We show that CD4+ CD25+ Treg cells from either TGF-beta1+/+ or neonatal TGF-beta1-/- mice can suppress the incidence and severity of IBD as well as colonic IFN-gamma mRNA expression induced by WT CD4+ CD25- effector T cells. Furthermore, TGF-beta-resistant Smad3-/- CD4+ CD25+ Treg cells are equivalent to WT Treg cells in their capacity to suppress disease induced by either WT or Smad3-/- CD4+ CD25- effector T cells. Finally, anti-TGF-beta treatment exacerbates the colitogenic potential of CD4+ CD25- effector T cells in the absence of CD4+ CD25+ Treg cells. Together, these data demonstrate that in certain situations CD4+ CD25+ T cells are able to suppress intestinal inflammation by a mechanism not requiring Treg cell-derived TGF-beta1 or effector T cell/Treg cell responsiveness to TGF-beta via Smad3.

Authors+Show Affiliations

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16180248

Citation

Kullberg, Marika C., et al. "TGF-beta1 Production By CD4+ CD25+ Regulatory T Cells Is Not Essential for Suppression of Intestinal Inflammation." European Journal of Immunology, vol. 35, no. 10, 2005, pp. 2886-95.
Kullberg MC, Hay V, Cheever AW, et al. TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. Eur J Immunol. 2005;35(10):2886-95.
Kullberg, M. C., Hay, V., Cheever, A. W., Mamura, M., Sher, A., Letterio, J. J., ... Piccirillo, C. A. (2005). TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. European Journal of Immunology, 35(10), pp. 2886-95.
Kullberg MC, et al. TGF-beta1 Production By CD4+ CD25+ Regulatory T Cells Is Not Essential for Suppression of Intestinal Inflammation. Eur J Immunol. 2005;35(10):2886-95. PubMed PMID: 16180248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. AU - Kullberg,Marika C, AU - Hay,Valerie, AU - Cheever,Allen W, AU - Mamura,Mizuko, AU - Sher,Alan, AU - Letterio,John J, AU - Shevach,Ethan M, AU - Piccirillo,Ciriaco A, PY - 2005/9/24/pubmed PY - 2005/12/13/medline PY - 2005/9/24/entrez SP - 2886 EP - 95 JF - European journal of immunology JO - Eur. J. Immunol. VL - 35 IS - 10 N2 - Naturally occurring CD4+ CD25+ regulatory T cells (Treg) are potent suppressors of CD4+ and CD8+ T cell responses in vitro and inhibit several organ-specific autoimmune diseases. While most in vitro studies suggest that CD4+ CD25+ Treg cells adopt a cytokine-independent but cell contact-dependent mode of T cell regulation, their precise mechanism of suppression in vivo remains largely unknown. Here we examine the functional contribution of Treg cell-derived TGF-beta1 and effector T cell responsiveness to TGF-beta in CD4+ CD25+ T cell-mediated suppression of inflammatory bowel disease (IBD). We show that CD4+ CD25+ Treg cells from either TGF-beta1+/+ or neonatal TGF-beta1-/- mice can suppress the incidence and severity of IBD as well as colonic IFN-gamma mRNA expression induced by WT CD4+ CD25- effector T cells. Furthermore, TGF-beta-resistant Smad3-/- CD4+ CD25+ Treg cells are equivalent to WT Treg cells in their capacity to suppress disease induced by either WT or Smad3-/- CD4+ CD25- effector T cells. Finally, anti-TGF-beta treatment exacerbates the colitogenic potential of CD4+ CD25- effector T cells in the absence of CD4+ CD25+ Treg cells. Together, these data demonstrate that in certain situations CD4+ CD25+ T cells are able to suppress intestinal inflammation by a mechanism not requiring Treg cell-derived TGF-beta1 or effector T cell/Treg cell responsiveness to TGF-beta via Smad3. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/16180248/TGF_beta1_production_by_CD4+_CD25+_regulatory_T_cells_is_not_essential_for_suppression_of_intestinal_inflammation_ L2 - https://doi.org/10.1002/eji.200526106 DB - PRIME DP - Unbound Medicine ER -