The MHC influences NK and NKT cell functions associated with immune abnormalities and lifespan

The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2(m)) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2(k)) strain has an MST of 24 months. It was previously shown that B10.AKM mice at 13-15 months of age have immunological function comparable to those of B10.BR mice at 22-26 months of age. These functions include: a low proliferative response, reduced levels of intracellular calcium release [Ca2+](i), and an increase in the frequency of memory helper T-cells (CD4(+) CD44(hi)CD45RB(lo)). In this report similar deficiencies were demonstrated in B10.AKM mice at 2-4 months of age and show that activated spleen NK1.1(+)CD4(+) T (NKT) cells from young B10.AKM mice produce a significantly higher level of IL-4 but a lower level of IFN-gamma as compared to NKT cells from B10.BR mice of the same age. Also, the cytotoxic activity of natural killer (NK) cells from spleens of young (2-4 months) as well as adult (12-16 months) B10.AKM mice is significantly lower (P < 0.01) than that of NK cells from B10.BR mice. These findings suggest that the NKT activity in young B10.AKM mice is a factor for the early onset of immune dysfunction leading to a shorter lifespan. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.