Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice.
The in vivo mechanism of regulatory T cell (T(reg) cell) function in controlling autoimmunity remains controversial. Here we have used two-photon laser-scanning microscopy to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of T(reg) cell control of autoimmunity in vivo. Islet antigen-specific CD4(+)CD25(-) T helper cells (T(H) cells) and T(reg) cells swarmed and arrested in the presence of autoantigens. These T(H) cell activities were progressively inhibited in the presence of increasing numbers of T(reg) cells. There were no detectable stable associations between T(reg) and T(H) cells during active suppression. In contrast, T(reg) cells directly interacted with dendritic cells bearing islet antigen. Such persistent T(reg) cell-dendritic cell contacts preceded the inhibition of T(H) cell activation by dendritic cells, supporting the idea that dendritic cells are central to T(reg) cell function in vivo.
Tang
Qizhi
Q
Diabetes Center, Department of Medicine, University of California, San Francisco 94143, USA.
Adams
Jason Y
JY
Tooley
Aaron J
AJ
Bi
Mingying
M
Fife
Brian T
BT
Serra
Pau
P
Santamaria
Pere
P
Locksley
Richard M
RM
Krummel
Matthew F
MF
Bluestone
Jeffrey A
JA
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010179:Pancreas / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism