The nature of triggers activating auto-aggressive lymphocytes in Multiple Sclerosis is poorly understood, but both environmental and genetic factors are relevant. The role of infectious agents in the regulation of antigen-specific T cell trafficking is currently unknown. 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 NSP 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. We show that early relocation associated with intermediate expression of CD44, a molecule controlling T cell migration under inflammatory conditions. TLR2 directly regulates the distribution of CD44 and the expression of its isoforms. Our results show that pathogens engaging TLR2 on activated T cells through a polymorphic site modulate expression of CD44 and regulate effector T cells trafficking in vivo.
Event Abstract Back to Event Impact of infectious agents on trafficking of effector T cells is mediated by a polymorphic site of TLR2 and CD44 isoforms expression
DI SANTE G;
2013
Abstract
The nature of triggers activating auto-aggressive lymphocytes in Multiple Sclerosis is poorly understood, but both environmental and genetic factors are relevant. The role of infectious agents in the regulation of antigen-specific T cell trafficking is currently unknown. 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 NSP 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. We show that early relocation associated with intermediate expression of CD44, a molecule controlling T cell migration under inflammatory conditions. TLR2 directly regulates the distribution of CD44 and the expression of its isoforms. Our results show that pathogens engaging TLR2 on activated T cells through a polymorphic site modulate expression of CD44 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.