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INFLAMMATION/IMMUNITY/MEDIATORS

Induction of CD8⁺ regulatory T cells in the intestine by Heligmosomoides polygyrus infection

¹Division of Gastroenterology-Hepatology, Department of Internal Medicine, Tufts-New England Medical Center, Boston, Massachusetts; ²Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland; and ³Department of Internal Medicine, University of Iowa, Iowa City, Iowa

Submitted 30 August 2005 ; accepted in final form 4 April 2006

This study determined whether Heligmosomoides polygyrus induces intestinal regulatory T cells. Splenic T cells proliferate strongly when cultured with anti-CD3 and antigen-presenting cells (APC). Lamina propria T cells from mice with H. polygyrus mixed with normal splenic T cells from uninfected mice inhibited proliferation over 90%. Lamina propria T cells from mice without H. polygyrus only modestly affected T cell proliferation. The worm-induced regulatory T cell was CD8⁺ and required splenic T cell contact to inhibit proliferation. The regulation also was IL-10 independent, but TAP-dependent, suggesting that it requires major histocompatibility complex (MHC) class I interaction. Additional studies employed mice with transgenic T cells that did not express functional TGF- receptors. The lamina propria T regulator inhibited proliferation of these transgenic T cells nearly 100%, suggesting that TGF- signaling via the T cell was not required. CD8⁺ T cells were needed for worms to reverse piroxicam-induced colitis in Rag mice (T and B cell deficient) reconstituted with IL-10^–/– T cells. Thus H. polygyrus induces a regulatory CD8⁺ lamina propria T cell that inhibits T cell proliferation and that appears to have a role in control of colitis.

inflammatory bowel disease; helminths; T cells; lamina propria

This article has been cited by other articles:

				I. A. Khan, R. Hakak, K. Eberle, P. Sayles, L. M. Weiss, and J. F. Urban Jr. Coinfection with Heligmosomoides polygyrus Fails To Establish CD8+ T-Cell Immunity against Toxoplasma gondii Infect. Immun., March 1, 2008; 76(3): 1305 - 1313. [Abstract] [Full Text] [PDF]

				T. Setiawan, A. Metwali, A. M. Blum, M. N. Ince, J. F. Urban Jr., D. E. Elliott, and J. V. Weinstock Heligmosomoides polygyrus Promotes Regulatory T-Cell Cytokine Production in the Murine Normal Distal Intestine Infect. Immun., September 1, 2007; 75(9): 4655 - 4663. [Abstract] [Full Text] [PDF]