Involvement of infectious agents on trafficking of effector T cells is mediated by a polymorphic site of TLR2 and CD44 isoforms expression

The role of infectious agents in the regulation of antigen-specific T cell trafficking seems to be linked with the triggering mechanisms of autoimmune disease. In our previous work, using a mouse model of Multiple Sclerosis (EAE), we showed that the amount of M tuberculosis in the adjuvant modulates rapid relocation of antigen-specific T cells from draining lymph nodes (LN) to spleen, in the SJL mouse. We observed that the modulation of T cell mobilization was strain dependent and linked to a SNP of Tlr2 responsible for early/late relocation phenotype. To clarify the mechanisms controlling early and late mobilization of T cells we examined the expression of activation markers and adhesion molecules involved in T cell trafficking. Performing in vitro and ex-vivo experiments we found that early relocation associated with mRNA and surface expression of CD44, a marker of T cell activation as well as adhesion molecule controlling T cell migration under inflammatory conditions. Tlr2 polymorphism besides conditioning T-cell mobility, EAE clinical course and lesion distribution, directly regulates the distribution of CD44, the expression of its isoforms and the receptor of hyaluronan, collagen, osteopontin and other molecules involved in cell trafficking. Our results reveal that pathogens engaging Tlr2 on activated T cells through a polymorphic site modulate expression of activation/adhesion molecules and regulate effector T cells trafficking in vivo.