A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells

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A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells

F Powrie, J Carlino, MW Leach, S Mauze and RL Coffman
DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto 94304, USA.

A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed in severe combined immunodeficiency mice reconstituted with CD45RB(high) CD4+ splenic T cells and could be prevented by cotransfer of CD45RB(low) CD4+ T cells. Inhibition of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either the differentiation of function of protective cells as CD45RB(low) CD4+ cells from IL-4-deficient mice were fully effective. These results identify a subpopulation of peripheral CD4+ cells and TGF-beta as critical components of the natural immune regulatory mechanism, which prevents the development of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.
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Das, G., Augustine, M. M., Das, J., Bottomly, K., Ray, P., Ray, A. (2003). An important regulatory role for CD4+CD8alpha alpha T cells in the intestinal epithelial layer in the prevention of inflammatory bowel disease. Proc. Natl. Acad. Sci. USA 100: 5324-5329 [Abstract] [Full Text]
Oida, T., Zhang, X., Goto, M., Hachimura, S., Totsuka, M., Kaminogawa, S., Weiner, H. L. (2003). CD4+CD25- T Cells That Express Latency-Associated Peptide on the Surface Suppress CD4+CD45RBhigh-Induced Colitis by a TGF-{beta}-Dependent Mechanism. J. Immunol. 170: 2516-2522 [Abstract] [Full Text]
Barthlott, T., Kassiotis, G., Stockinger, B. (2003). T Cell Regulation as a Side Effect of Homeostasis and Competition. JEM 197: 451-460 [Abstract] [Full Text]
Maloy, K. J., Salaun, L., Cahill, R., Dougan, G., Saunders, N. J., Powrie, F. (2003). CD4+CD25+ TR Cells Suppress Innate Immune Pathology Through Cytokine-dependent Mechanisms. JEM 197: 111-119 [Abstract] [Full Text]
Kursar, M., Bonhagen, K., Fensterle, J., Kohler, A., Hurwitz, R., Kamradt, T., Kaufmann, S. H.E., Mittrucker, H.-W. (2002). Regulatory CD4+CD25+ T Cells Restrict Memory CD8+ T Cell Responses. JEM 196: 1585-1592 [Abstract] [Full Text]
Cong, Y., Weaver, C. T., Lazenby, A., Elson, C. O. (2002). Bacterial-Reactive T Regulatory Cells Inhibit Pathogenic Immune Responses to the Enteric Flora. J. Immunol. 169: 6112-6119 [Abstract] [Full Text]
Almeida, A. R. M., Legrand, N., Papiernik, M., Freitas, A. A. (2002). Homeostasis of Peripheral CD4+ T Cells: IL-2R{alpha} and IL-2 Shape a Population of Regulatory Cells That Controls CD4+ T Cell Numbers. J. Immunol. 169: 4850-4860 [Abstract] [Full Text]