title: Role of the CD5 molecule on TCR gammadelta T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation.
abstract: Although CD4(+) T cells form a major subset of TCRalphabeta T cells, only a small number of TCRgammadelta T cells express CD4. Factors contributing to the down-regulation of CD4(+) TCRgammadelta T cells have not been identified. The CD5 molecule is expressed on most TCRgammadelta T cells in the spleen, whereas only a few intestinal intraepithelial TCRgammadelta T cells express this molecule in wild-type mice and TCRbeta mutant (beta(-/-)) mice. Unexpectedly, in the present studies, the lack of CD5 led to a remarkable increase of a CD4(+) TCRgammadelta T cell subset in CD5(-/-)beta(-/-) mice. The CD4(+) TCRgammadelta T cells were also detectable in MHC II(-/-)CD5(-/-)beta(-/-) triple-mutant mice. This CD4(+) TCRgammadelta T cell subset provided help in Mycobacterium-induced germinal center (GC) formation and showed a T(h)-like cytokine profile. In contrast, CD5(+) TCRgammadelta T cells suppressed the CD4(+) TCRgammadelta T cell-mediated GC formation, presumably by eliminating this CD4(+) subset. Unlike intraepithelial gammadelta T cells, >30% of TCRgammadelta T cells in the colonic lamina propria (LP) expressed CD5. The lack of CD5 also led to increased numbers of CD4(+) TCRgammadelta T cells in the colonic LP and increased susceptibility to development of chronic colitis in beta(-/-) mice. Cell transfer studies suggest that CD5(+) TCRgammadelta T cells are capable of selectively eliminating CD4(+) TCRgammadelta T cells in the intestine. The CD4(+) TCRgammadelta T cells possess immune functions similar to CD4(+) TCRalphabeta T cells.
authors.affiliation: Department of Pathology and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA. amizoguchi@partners.org
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: Ype P
authors.initials: YP
authors.lastname: de Jong
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takedatsu
authors.forename: Frederic I
authors.initials: FI
authors.lastname: Preffer
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000276:immunology*; D002908:Chronic Disease; D004198:Disease Susceptibility; D018858:Germinal Center / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D007249:Inflammation; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D018956:CD5 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta