TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype - PubMed (original) (raw)
TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype
C King et al. Immunity. 1998 May.
Free article
Abstract
TGF-beta1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-beta1 mice relied on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antigen, whereas T cells from ins-TGF-beta1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4 antibody, islet antigen-specific IFNGamma-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This suggests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-beta1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.
Similar articles
- Pancreatic IL-4 expression results in islet-reactive Th2 cells that inhibit diabetogenic lymphocytes in the nonobese diabetic mouse.
Gallichan WS, Balasa B, Davies JD, Sarvetnick N. Gallichan WS, et al. J Immunol. 1999 Aug 1;163(3):1696-703. J Immunol. 1999. PMID: 10415077 - Determinant spreading of T helper cell 2 (Th2) responses to pancreatic islet autoantigens.
Tian J, Lehmann PV, Kaufman DL. Tian J, et al. J Exp Med. 1997 Dec 15;186(12):2039-43. doi: 10.1084/jem.186.12.2039. J Exp Med. 1997. PMID: 9396773 Free PMC article. - Cellular and molecular pathogenic mechanisms of insulin-dependent diabetes mellitus.
Yoon JW, Jun HS. Yoon JW, et al. Ann N Y Acad Sci. 2001 Apr;928:200-11. doi: 10.1111/j.1749-6632.2001.tb05650.x. Ann N Y Acad Sci. 2001. PMID: 11795511 Review. - Glutamic acid decarboxylase and other autoantigens in IDDM.
Nepom GT. Nepom GT. Curr Opin Immunol. 1995 Dec;7(6):825-30. doi: 10.1016/0952-7915(95)80055-7. Curr Opin Immunol. 1995. PMID: 8679127 Review.
Cited by
- Mechanobiology of immune cells: Messengers, receivers and followers in leishmaniasis aiding synthetic devices.
Khandibharad S, Nimsarkar P, Singh S. Khandibharad S, et al. Curr Res Immunol. 2022 Aug 23;3:186-198. doi: 10.1016/j.crimmu.2022.08.007. eCollection 2022. Curr Res Immunol. 2022. PMID: 36051499 Free PMC article. Review. - Immune Inhibitory Properties and Therapeutic Prospects of Transforming Growth Factor-Beta and Interleukin 10 in Autoimmune Hepatitis.
Czaja AJ. Czaja AJ. Dig Dis Sci. 2022 Apr;67(4):1163-1186. doi: 10.1007/s10620-021-06968-6. Epub 2021 Apr 9. Dig Dis Sci. 2022. PMID: 33835375 Review. - Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets.
Lu J, Liu J, Li L, Lan Y, Liang Y. Lu J, et al. Clin Transl Immunology. 2020 Mar 16;9(3):e1122. doi: 10.1002/cti2.1122. eCollection 2020. Clin Transl Immunology. 2020. PMID: 32185024 Free PMC article. Review. - Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection.
Sanjabi S, Oh SA, Li MO. Sanjabi S, et al. Cold Spring Harb Perspect Biol. 2017 Jun 1;9(6):a022236. doi: 10.1101/cshperspect.a022236. Cold Spring Harb Perspect Biol. 2017. PMID: 28108486 Free PMC article. Review. - Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes.
Kaminitz A, Ash S, Askenasy N. Kaminitz A, et al. Clin Rev Allergy Immunol. 2017 Jun;52(3):460-472. doi: 10.1007/s12016-016-8587-y. Clin Rev Allergy Immunol. 2017. PMID: 27677500 Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases