CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression, and tissue invasion.
It is well established that CD4(+)CD25(+) regulatory T cells (Tregs) inhibit autoimmune pathology. However, precisely how the behavior of disease-inducing T cells is altered by Tregs remains unclear. In this study we use a TCR transgenic model of diabetes to pinpoint how pathogenic CD4 T cells are modified by Tregs in vivo. We show that although Tregs only modestly inhibit CD4 cell expansion, they potently suppress tissue infiltration. This is associated with a failure of CD4 cells to differentiate into effector cells and to up-regulate the IFN-gamma-dependent chemokine receptor CXCR-3, which confers the ability to respond to pancreatic islet-derived CXCL10. Our data support a model in which Tregs permit T cell activation, yet prohibit T cell differentiation and migration into Ag-bearing tissues.
Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.
Nadia
N
Sarween
Anna
A
Chodos
Chandra
C
Raykundalia
Mahmood
M
Khan
Abul K
AK
Abbas
Lucy S K
LS
Walker
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000235:genetics; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*
C515188:Cxcr3 protein, mouse; D016207:Cytokines; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma