Background:  The most consistent hypothesis to explain the slow progression of progressive multifocal leukoencephalopathy (PML) observed in HAART-treated HIV⁺ patients is that the reconstitution of the immune system may restore immune defenses against JC virus (JCV), leading the patients to a longer survival time. However, in apparent contrast, it has also been observed that, in a very few cases, the introduction of HAART can contribute, probably through an autoimmune mechanism, both to induce new demyelinating lesions and to worsen the prognosis of already diagnosed PML and not determined leukoencephalopathy (NDLE), a PML-like JCV-negative disorder. A possible explanation of controversial effect of immune reconstitution could be that immune-competent cells switch their activity, probably through molecular mimicry with cross-reacting JCV epitopes, also against self-component such as myelin basic protein (MBP). As suggested from studies on autoimmune disorders, such as multiple sclerosis (MS), a deregulation of apoptosis could play a key role in inducing or maintaining auto-reactive immune phenomenon. Thus, in NDLE and PML patients, an imbalance of apoptosis could lead to autoimmune demyelination mechanism.

Methods:  In our study, we analyzed by flow cytometry IL2 IFN-g-producing CD4⁺ and TNF-a IFN-g-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 MS patients, and 14 healthy controls (HC). Differences were analyzed by Student’s test.

Results:  A significant increase of IFN-g-producing CD8⁺ T cell was observed in PML and relapsing-remitting MS patients in comparison with HC (p <0.05), and increasing of CD8⁺ apoptotic cells in HC compared to MS, NDLE, and PML patients (p <0.05). High proliferation index (>2) was shown in 2 NDLE, 1 PML, and 3 MS patients.

Conclusions:  The obtained data evidenced specific activation of immune system against self-antigen, such as MBP in patients with leukoencephalopathies and MS, together with a decrease of CD8⁺ apoptotic MBP-specific T cells in the same patients. On the whole, it could be suggested that the auto-reactive immune phenomena could play a role in PML, NDLE, and MS.