NKT cells inhibit the onset of diabetes by impairing the development of pathogenic T cells specific for pancreatic beta cells.
To determine the precise regulatory effect of NKT cells on CD4(+) T cells involved in autoimmune diabetes, we developed an in vivo model in which transferred naive transgenic T cells are stimulated by their antigen in the presence or absence of NKT cells or in the presence of another conventional transgenic alphabeta T cell. The presence of NKT cells did not block the initial activation and expansion of the CD4(+) T cells but did inhibit their IL-2 and IFN-gamma production and later proliferation, resulting in an anergic phenotype. These CD4(+) T cells did not induce significant insulitis and were unable to destroy the beta cells. Thus, NKT cells prevent alphabeta CD4 T cell differentiation into effector cells.
Beaudoin
Lucie
L
INSERM U561, Hôpital Cochin-Saint Vincent de Paul, 75014, Paris, France.
Laloux
Véronique
V
Novak
Jan
J
Lucas
Bruno
B
Lehuen
Agnès
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007111:Immunity, Cellular; D007515:Islets of Langerhans / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta