Programmed cell death and expression of apoptotic genes in PBMC from multiple sclerosis patients

Recently we demonstrated that in Multiple Sclerosis (MS) a deregulation of programmed cell death (PCD) or apoptosis plays a key role in inducing or maintaining auto-reactive immune phenomenon leading to the development of demyelinating lesions. In the present study we investigated the PCD of myelin basic protein (MBP)-specific T lymphocytes in 47 Relapsing-remitting (RR) MS patients, 29 with acute (AMS) and 18 with stable MS (SMS), together with 30 Healthy Controls (HC). In particular, we analyzed by flow cytometry CD4+ and CD8+ apoptotic and CD3+ proliferating cell percentage, and by RT PCR the expression of different anti (FLIP, XIAP, Bcl-2) and pro (BID, APAF-1) apoptotic genes in sorted CD4+ and CD8+ T cells, previously stimulated with MBP peptides. Differences were analyzed by t-Student and Mann-Whitney tests. The percentage of apoptotic MBP specific CD4+ and CD8+ T cells decreased in AMS compared to SMS (p < 0.05) and HC (p < 0.05). Conversely, an higher proliferation index of MBP specific T cells was found in AMS and HC compared to SMS (p < 0.05). An higher expression, even thought no statistically significant, of both anti and pro apoptotic genes was shown in RRMS compared to HC; in addition, a significant increase of anti apoptotic genes FLIP, XIAP and Bcl-2 was observed in MBP- specific sorted CD8+ cells of AMS compared to HC. The data obtained evidence a specific activation of immune system against MBP in patients with AMS and in HC, but the increase of PCD in HC switch off the MBP specific T cell immune response. Conversely in AMS, the decrease of apoptotic MBP specific T cell seems to be involved in the immune mediated destruction of myelin sheath.