Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection.
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-beta receptors. The lamina propria T regulator inhibited proliferation of these transgenic T cells nearly 100%, suggesting that TGF-beta 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.
Metwali
Ahmed
A
Department of Internal Medicine, University of Iowa, Iowa City, USA.
Setiawan
Tommy
T
Blum
Arthur M
AM
Urban
Joseph
J
Elliott
David E
DE
Hang
Long
L
Weinstock
Joel V
JV
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003092:Colitis / Q000276:immunology* / Q000469:parasitology; D007422:Intestines / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius; D017206:Strongylida Infections / Q000276:immunology* / Q000473:pathology*