L-selectin and beta7 integrin on donor CD4 T cells are required for the early migration to host mesenteric lymph nodes and acute colitis of graft-versus-host disease.
The homing receptors L-selectin and alpha4beta7 integrin facilitate entry of T cells into the gut-associated organized lymphoid tissues such as the mesenteric lymph nodes and Peyer patches. We studied the impact of inactivation of genes encoding these receptors on the ability of purified donor CD4+ T cells to induce acute lethal graft-versus-host disease (GVHD) associated with severe colitis in irradiated major histocompatibility complex (MHC)-mismatched mice. Whereas lack of expression of a single receptor had no significant impact on the severity of colitis and GVHD, the lack of expression of both receptors markedly ameliorated colitis and early deaths observed with wild-type (WT) T cells. The changes in colitis and GVHD were reflected in a marked reduction in the early accumulation of donor T cells in the mesenteric lymph nodes and subsequently in the colon. The purified WT donor CD4+ T cells did not accumulate early in the Peyer patches and failed to induce acute injury to the small intestine. In conclusion, the combination of CD62L and beta7 integrin is required to induce acute colitis and facilitate entry of CD4+ donor T cells in the mesenteric nodes associated with lethal GVHD in allogeneic hosts.
Dutt
Suparna
S
Department of Medicine, Stanford University School of Medicine, CCSR Building, Room 2215-C, Pasteur Drive, Stanford, CA 94305-5166, USA.
Ermann
Joerg
J
Tseng
Diane
D
Liu
Yin Ping
YP
George
Tracy I
TI
Fathman
C Garrison
CG
Strober
Samuel
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D003092:Colitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology* / Q000473:pathology; D039641:Integrin beta Chains / Q000276:immunology / Q000378:metabolism*; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000276:immunology; D051379:Mice
D039641:Integrin beta Chains; C091368:integrin beta7; D019041:L-Selectin