Dispensable role of chemokine receptors in migration of mycobacterial antigen-specific CD4+ T cells into mycobacteria-infected lung

Abstract

Abstract Mycobacterial antigen-specific CD4+ Th1 cells have a pivotal role in protective immunity against mycobacterial infections, including pulmonary tuberculosis. In the course of infection, Th1 cells differentiate in the lung-draining lymph nodes and migrate into the infected lung. Chemokine receptors on T cells are involved in T cell migration into the intestine and skin. However, the role of chemokine receptors in the migration of CD4+ T cells into the lung has not yet been determined. To address this issue, the role of chemokine receptors in T cell migration into the mycobacteria-infected lung was analyzed using mycobacterial Ag85B peptide 25-specific T cell receptor-transgenic (P25) CD4+ T cells. P25 T cells in the Mycobacterium bovis BCG-infected lung and lung-draining mediastinal lymph nodes (MedLN) expressed the chemokine receptors, CCR5, CCR6, CXCR3, and CXCR5, which bind chemokines produced by the BCG-infected lung. To further analyze the role of chemokine receptors in the migration of BCG-primed P25 T cells into the lung and medLN, P25 T cells were adoptively transferred into BCG-infected wild-type mice and their migration into the lung was monitored. Unexpectedly, blocking chemokine receptor function with pertussis toxin, a G-protein inhibitor, failed to suppress migration of T cells into the infected lung. However, the treatment completely blocked migration of the MedLN P25 T cells into the recipient lymph node. These results suggest that the interaction of chemokine receptors on mycobacterial antigen-specific Th1 cells with chemokines is dispensable for their migration into the mycobacteria-infected lung.