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.
Fallarino
Francesca
F
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
Grohmann
Ursula
U
Hwang
Kwang Woo
KW
Orabona
Ciriana
C
Vacca
Carmine
C
Bianchi
Roberta
R
Belladonna
Maria Laura
ML
Fioretti
Maria Cristina
MC
Alegre
Maria-Luisa
ML
Puccetti
Paolo
P
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