Activated CD1d-restricted natural killer T cells secrete IL-2: innate help for CD4+CD25+ regulatory T cells?
CD4(+)CD25(+) and CD1d-restricted natural killer T (NKT) cells are thymus-derived self-reactive regulatory T cells that play a key role in the control of pathological immune responses. Little is known about functional cooperation between innate regulatory NKT cells and adaptive CD4(+)CD25(+) regulatory cells. Here we show that human CD4(+)Valpha24(+)Vbeta11(+) (CD4(+) NKT) cells isolated from peripheral blood by flow cytometric cell sorting secrete substantial amounts of IL-2 after stimulation with dendritic cells (DC) and alpha-Galactosylceramide. When cocultured with CD4(+)CD25(+) cells, CD4(+) NKT cells promoted moderate proliferation of CD4(+)CD25(+) cells. The proliferation of CD4(+)CD25(+) T cells was due to soluble IL-2 produced by activated CD4(+) NKT cells. The expanded CD4(+)CD25(+) cells remained anergic and retained their potent suppressive properties. These findings indicate that unlike conventional CD4(+) and CD8(+) T cells, which are susceptible to CD4(+)CD25(+) regulatory cell suppression, NKT cells promote CD4(+)CD25(+) regulatory cell proliferation. These data raise the possibility that NKT cells can function as helper cells to CD4(+)CD25(+) regulatory T cells, thereby providing a link between the two naturally occurring populations of regulatory T cells.
Jiang
Shuiping
S
Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, UK. shuiping.jiang@kcl.ac.uk
Game
David S
DS
Davies
Derek
D
Lombardi
Giovanna
G
Lechler
Robert I
RI
D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D007376:Interleukin-2; D015375:Receptors, Interleukin-2