RECIPROCAL REGULATION OF PROTEIN-TYROSINE KINASES P56(LCK) AND P59(FYN), AND ALTERED TYROSINE PHOSPHORYLATION IN MURINE AIDS

Murine AIDS (MAIDS), caused by a defective murine leukemia virus, is a severe lymphoproliferative disease associated with profound immunodef iciency and increased susceptibility to opportunistic infections. Most subsets of lymphocytes, including CD4(+) and CD8(+) T cells, are refr actory to mitogen stimulation. As a first step to examine proximal sig nal transduction in the infected mice, Western and Northern blot analy ses were performed, and showed that p56(lck) is dramatically decreased at the protein as well as the mRNA level in the lymph nodes (LN). In contrast, p59(fyn) and its mRNA were slightly increased in the LN of t he same mice. Similar results were obtained with purified T cells, Int erestingly, the thymus of the infected animals did not show any abnorm ality regarding p56(lck) or p59(fyn), Tyrosine phosphorylation was con stitutively increased in the infected mice and was barely amplified by anti-CD3 mAb stimulation. A similar pattern was observed when tyrosin e phosphorylation was selectively examined at the level of ZAP-70. Our results suggest that a reciprocal regulation of p56(lck) and p59(fyn) protein tyrosine kinases, previously described in various models of a nergy, could also be involved in the pathogenesis of MAIDS.