Demonstration of strong enterobacterial reactivity of CD4+CD25- T cells from conventional and germ-free mice which is counter-regulated by CD4+CD25+ T cells.
Unfractionated CD4+ T cells from the gut-associated lymphoid tissue (GALT) and peripheral lymph nodes are unresponsive when exposed to enterobacterial antigens in vitro. Under similar conditions, CD4+ T cells depleted in vivo or in vitro of CD4+CD25+ T cells proliferate extensively. The CD4+CD25- T cell reactivity depends on MHC class II presentation, specific TCR stimulation, CD4 ligation, and antigen processing by antigen-presenting cells. The CD4+CD25- T cells respond to autologous and heterologous enterobacterial antigens, but not to antigens from the feces of germ-free mice. Surprisingly, CD4+CD25- T cells obtained from the GALT of germ-free mice also proliferate when exposed to enterobacterial antigens, and adding back the conventional or germ-free CD4+CD25+ T cells to the enteroantigen-stimulated CD4+CD25- T cells abolishes proliferation. As judged from carboxyfluorescein diacetate succinimidyl ester-labeling experiments, 4-5% of the CD4+CD25- T cells respond to enteroantigen. The data show for the first time that CD4+CD25- T cells with reactivity towards the enterobacterial flora and regulatory CD4+CD25- T cells are present in both conventional and germ-free mice. The data suggest that a significant proportion of the peripheral pool of CD4+CD25- T cells express anti-enterobacterial reactivity, which, due to the presence of regulatory CD4+CD25+ T cells, is kept in a quiescent state.
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Monika
M
Gad
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Anders Elm
AE
Pedersen
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Nanna N
NN
Kristensen
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Mogens H
MH
Claesson
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2