Analysis of T cells repertoire and clinical course of EAE after pretreatment with CNS antigens with asymmetric liposomes

Objective: Experimental Autoimmune Encephalomyelitis (EAE) is the murine model of Multiple Sclerosis. Phospholipids have been shown to effectively modulate the immune response. We studied the effect of asymmetric liposomes on recruitment of CNS-specific T lymphocytes in EAE and on disease clinical course. Methods: T cell repertoire analysis: Female SJL mice were pretreated s.c. with liposomes with or without PLP139-151. Mice were immunized s.c. 15 days after pretreatment with PLP139-151 in PBS emulsified 1:1 in CFA. Ten days later T cells from draining lymph nodes were cultured in the presence or absence of PLP139 for 3 days. The analysis of specific TCR-β repertoire were performed using immunoscope technique (Ria et al. 2006). EAE induction: Female SJL mice were pretreated s.c. with liposomes or with plp139-151 and liposomes and were immunized 15 days after to induce EAE with PLP139-151 emulsified 1:1 with CFA 4x. Clinical score was evaluated following published criteria (Touhy et al. 1988). Results: The immunoscope analysis of the PLP139-151 specific TR-β repertoire showed some interesting results: mice treated with Liposomes and PLP 139-151 recruited less frequently CD4+ T cells carrying the semiprivate rearrangement VB4-Jb1.6 than mice of the control group; There were no differences in the recruitment of CD4+ T cells carrying the public rearrangement VB10-Jb1.1. Furthermore, administration of Liposomes and PLP139-151 decreased usage of CD8+ cells carrying the public and semi-private rearrangements VB17-Jb1.6 and VB20-Jb2.3. Surprisingly we observed that the pre-immune TCR-β repertoire, which is usually depleted after immunization with PLP (Penitente et al. 2008), was still preserved in the group of mice pretreated with Liposomes and PLP 139-151. When EAE was induced after pre-treatment with liposomes in the presence or absence of PLP139-151, We observed a significant difference in the clinical score of the disease. In particular the group of mice previously treated with Liposomes + PLP139-151 presented a lower severity of the symptoms at the onset of the disease. Conclusions: Although the observed differences in the recruitment of T lymphocytes can justify the different clinical course of the disease, further studies are needed to understand the mechanism through which co-administration of antigens with asymmetric liposomes modifies immune responses.