Inhibition of T cell differentiation into effectors by NKT cells requires cell contacts.
NKT cells are potent regulatory T cells that prevent the development of several autoimmune diseases. Analysis of NKT cell regulatory function in the NOD mouse has revealed that NKT cells inhibit the development of type 1 diabetes by impairing the differentiation of anti-islet T cells into Th1 effector cells. In the present study, we have performed in vitro and in vivo experiments to determine the respective role of cytokines and cell contacts in the blockade of T cell differentiation by NKT cells. These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-beta, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-beta. In contrast, we show for the first time that cell contacts are crucial for the immunoregulatory function of NKT cells.
Novak
Jan
J
Institut National de la Santé de la Recherche Médicale Unité 561, Hôpital Cochin-Saint Vincent de Paul, 82 Avenue Denfert-Rochereau, 75014 Paris, France.
Beaudoin
Lucie
L
Griseri
Thibault
T
Lehuen
Agnès
A
D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D018793:Interleukin-13; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4