[en] Murine AIDS (MAIDS), caused by a defective murine leukemia virus, is a severe lymphoproliferative disease associated with profound immunodeficiency and increased susceptibility to opportunistic infections. Most subsets of lymphocytes, including CD4+ and CD8+ T cells, are refractory to mitogen stimulation. As a first step to examine proximal signal transduction in the infected mice, Western and Northern blot analyses were performed, and showed that p56lck 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 the same mice. Similar results were obtained with purified T cells. Interestingly, the thymus of the infected animals did not show any abnormality regarding p56(lck) or p59(fyn). Tyrosine phosphorylation was constitutively increased in the infected mice and was barely amplified by anti-CD3 mAb stimulation. A similar pattern was observed when tyrosine 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 anergy, could also be involved in the pathogenesis of MAIDS.
Disciplines :
Immunology & infectious disease
Author, co-author :
Trebak, Mohamed
Lambert, Chantal ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Rahmouni, Souad ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Greimers, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Boniver, Jacques ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Moutschen, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Maladies infectieuses et médecine interne générale
Language :
English
Title :
Reciprocal regulation of protein tyrosine kinases p56lck and p59fyn, and altered tyrosine phosphorylation in murine AIDS.
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