Modulation of NKT cell development by B7-CD28 interaction: an expanding horizon for costimulation.
It has been demonstrated that the development of NKT cells requires CD1d. The contribution of costimulatory molecules in this process has not been studied. Here we show that in mice with targeted mutations of B7-1/2 and CD28, the TCRbeta(+)alpha-Galcer/CD1d(+) (iValpha14 NKT) subset is significantly reduced in the thymus, spleen and liver. This is mainly due to decreased cell proliferation; although increased cell death in the thymi of CD28-deficient mice was also observed. Moreover, in the B7-1/2- and CD28-deficient mice, we found a decreased percentage of the CD4(-)NK1.1(+) subset and a correspondingly increased portion of the CD4(+)NK1.1(-) subset. In addition, the mice with a targeted mutation of either B7 or CD28 had a reduced susceptibility to Con A induced hepatitis, which is known to be mediated by NKT cells. Our results demonstrate that the development, maturation and function of NKT cell are modulated by the costimulatory pathway and thus expand the horizon of costimulation into NKT, which is widely viewed as a bridge between innate and adaptive immunity. As such, costimulation may modulate all major branches of cell-mediated immunity, including T cells, NK cells and NKT cells.
Zheng
Xincheng
X
Department of Surgery, Comprehensive Cancer Center, Program of Molecular Mechanism of Diseases, University of Michigan, Ann Arbor, Michigan, United States of America.
Zhang
Huiming
H
Yin
Lijie
L
Wang
Chyung-Ru
CR
Liu
Yang
Y
Zheng
Pan
P
D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D007371:Interferon-gamma