The most consistent hypothesis to explain the slow progression of PML observed in HAART treated patients is that the reconstitution of the immune system may restore immune defenses against JCV leading these patients to a longer survival time. However, in apparent contrast, it has also been observed that in a very limited number of cases the introduction of HAART can contribute, probably through an autoimmune mechanism, to induce new demyelinating lesions and to their increase in size in already diagnosed PML and in NDLE, a PML-like JCV negative disorders, patients. A possible explanation of controversial effect of immune reconstitution could be immune competent cells switch this activity, probably through molecular mimicry with cross-reacting JCV epitopes, also against self-component like Myelin Basic Protein (MBP). As suggested from observations derived from studies on autoimmune disorders, like Multiple Sclerosis (MS), a disregulation of apoptosis could play a key role in inducing or maintaining auto-reactive immune phenomenon. Thus in NDLE and in PML patients, an imbalance of apoptosis could lead to autoimmune demyelination mechanism. In our study we analyzed by flow cytometry IL2 IFNg producing CD4+ and TNFa IFNg producing CD8+ T cells, CD4+ and CD8+ proliferating cells and CD4+ CD8+ apoptotic cells after MBP stimulation in 8 PML, 14 NDLE, 20 Relapsing-remitting (RR) MS groups and 14 Healthy Control (HC). We observed a significant increase of IFNg producing CD8+ T cell in PML and RRMS patients in comparison to HC (p < 0.05), and of CD8+ apoptotic cell in HC in comparison to MS, NDLE and PML patients (p < 0.05). An higher proliferation index (>2) was shown in 2 NDLE, 1PML and 3 MS patients. These data evidence an activation of immune system against self antigen like MBP in patients with leukoencephalopathy and MS with a decrease of CD8+ apoptotic MBP specific T cells in the same patients. On the whole they suggest that these auto-reactive immune phenomenons could play a relevant role in PML, NDLE and MS.
|Titolo:||Apoptosis and immune response in peripheral blood cells after stimulation with myelin basic protein in HIV+ patients with leukoencephalopathy|
|Autori interni:||FERRANTE, PASQUALE|
|Parole Chiave:||Multiple sclerosis; Apoptosis; CD8 antigen; CD4 antigen; Lymphocytes T; highly active antiretroviral therapy; Myelin basic protein; Leukoencephalopathy; Immune system; Flow cytometry; Peripheral blood; Autoantigens; Immune response; Cell activation; Epitopes; Demyelination; Interleukin 2; Survival; Human immunodeficiency virus|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Data di pubblicazione:||2005|
|Appare nelle tipologie:||01 - Articolo su periodico|