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

2000; Elsevier BV; Volume: 113; Issue: 2 Linguagem: Inglês

10.1016/s0047-6374(99)00102-5

1872-6216

Devendra P. Dubey, Zaheed Husain, Edward Levitan, David Zurakowski, Nadeem Q. Mirza, Souhad Younes, Carlos Coronell, David Yunis, Juan J. Yunis,

T-cell and B-cell Immunology

The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2m) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2k) 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+CD44hiCD45RBlo). 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-γ 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.