Impact of infectious agents on trafficking of effector T cells is mediated by a polymorphic site of TLR2.

The role of infectious agents in the regulation of antigen-specific T cell trafficking is currently unknown. Here we report evidence that the amount of M tuberculosis in the adjuvant modulates rapid relocation of PLP139-151 (p139)-specific T cells carrying the public TCR-beta chain BV1-CASS SGS NTE JB1.1 from draining lymph nodes (LN) to spleen, in the SJL mouse. In fact, T cells of mice immunized in the presence of a low dose of M tuberculosis mostly reached the spleen by day 28 after immunization (“late relocation”), whereas a high dose of M tuberculosis in the adjuvant promoted relocation of T cells to the spleen already by d 14 after immunization (“early relocation”). Modulation of T cell mobilization was strain-dependent with the C57/Bl6 background conferring a dominant “early relocation” phenotype to F1 (SJL x C57/Bl6) mice, allowing early relocation of T cells to the spleen also in the presence of low dose M tuberculosis. T cells from F1 (SJL x C57/Bl6tlr2-) mice that displayed only functional TLR2 of SJL origin did not relocate to the spleen at day 14 post-immunization in the presence of low dose of M tuberculosis, suggesting that TLR2 of C57/Bl6 origin confers the early relocation phenotype to F1 (SJL x C57/Bl6) mice. One non-synonymous polymorphism exists between TLR2 of SJL and of C57/BL6. F1 (SJLxC57/Bl6) mice homozygous for TLR2 of SJL display the same “late relocation” phenotype of F1 (SJL x C57/Bl6tlr2-) heterozygous littermates, formally proving that this polymorphism is responsible for “early/late” relocation phenotype. By transferring T cells from F1 mice obtained crossing SJL mice transgenic for the mentioned TCR-beta chain of the p139-specific, public receptor (SJLBV10) with C57/Bl6wt or C57/Bl6tlr2-, we determined that egress of antigen specific lymphocytes is modulated directly by TLR2 expressed on T cells. 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. We show that early relocation associated with intermediate expression of CD44, a marker of T cell activation as well as adhesion molecule controlling T cell migration under inflammatory conditions. 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.