Background: The role of infectious agents in the regulation of T cell trafficking is currently unknown. Methods: We examined this issue using immunoscope and TCR transgenic mice. Results: The amount of M tuberculosis in the adjuvant modulates rapid relocation of PLP139-151 (p139)-specific T cells carrying a public TCR-beta chain BV10-CASS SGS NTE JB1.1 from draining lymph nodes (LN) to spleen in the SJL mouse. In the presence of low dose of M tuberculosis in the adjuvant, T cells mostly reach the spleen by day 28 after immunization (“late relocation”), whereas the same T cells reach the spleen by day 14 after immunization with high dose of M tuberculosis (“early relocation”). The B6 background confers a dominant “early relocation” phenotype to F1 (SJL x B6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 (Ile83Met) is responsible for “early/late” relocation phenotype. By transferring T cells from F1 mice obtained crossing SJL mice transgenic for the TCR-beta chain indicated above (SJLBV10) with C57/B6wt or C57/B6tlr2-, we determined that egress of antigen specific lymphocytes is modulated by TLR2 expressed on T cells. We also examined the expression of some markers regulated by activation and involved in T cell trafficking. Early relocation is associated with an intermediate expression of CD44 and that TLR2 also regulates processing of CD44 pre-mRNA. Conclusions: 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.
Mycobacterium tuberculosis in the Adjuvant Modulates Trafficking of Effector T Cells Through a Polymorphic Site of TLR2
DI SANTE G;
2012
Abstract
Background: The role of infectious agents in the regulation of T cell trafficking is currently unknown. Methods: We examined this issue using immunoscope and TCR transgenic mice. Results: The amount of M tuberculosis in the adjuvant modulates rapid relocation of PLP139-151 (p139)-specific T cells carrying a public TCR-beta chain BV10-CASS SGS NTE JB1.1 from draining lymph nodes (LN) to spleen in the SJL mouse. In the presence of low dose of M tuberculosis in the adjuvant, T cells mostly reach the spleen by day 28 after immunization (“late relocation”), whereas the same T cells reach the spleen by day 14 after immunization with high dose of M tuberculosis (“early relocation”). The B6 background confers a dominant “early relocation” phenotype to F1 (SJL x B6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 (Ile83Met) is responsible for “early/late” relocation phenotype. By transferring T cells from F1 mice obtained crossing SJL mice transgenic for the TCR-beta chain indicated above (SJLBV10) with C57/B6wt or C57/B6tlr2-, we determined that egress of antigen specific lymphocytes is modulated by TLR2 expressed on T cells. We also examined the expression of some markers regulated by activation and involved in T cell trafficking. Early relocation is associated with an intermediate expression of CD44 and that TLR2 also regulates processing of CD44 pre-mRNA. Conclusions: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
