Modulation of tryptophan catabolism by regulatory T cells.
Regulatory T (T(R)) cells manifest constitutive expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating the regulatory function of T(R) cells is unclear. We show here that mouse CD4+CD25+ cells, either resting or induced to overexpress CTLA-4 by treatment with antibody to CD3, initiated tryptophan catabolism in dendritic cells through a CTLA-4-dependent mechanism. This process required B7 expression and cytokine production by the dendritic cells. In contrast, T(R) cells cultured in the presence of bacterial lipopolysaccharide induced tryptophan catabolism by dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus, regulation of immunosuppressive tryptophan catabolism in dendritic cells might represent a major mechanism of action of T(R) cells.
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
Francesca
F
Fallarino
Ursula
U
Grohmann
Kwang Woo
KW
Hwang
Ciriana
C
Orabona
Carmine
C
Vacca
Roberta
R
Bianchi
Maria Laura
ML
Belladonna
Maria Cristina
MC
Fioretti
Maria-Luisa
ML
Alegre
Paolo
P
Puccetti
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007108:Immune Tolerance; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000276:immunology / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D015375:Receptors, Interleukin-2; D014364:Tryptophan; D014366:Tryptophan Oxygenase