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

Abstract

Mycobacterial antigen-specific CD4+ Th1 cells have pivotal role in protective immunity against mycobacterial infections including pulmonary tuberculosis. In the course of the 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, role of chemokine receptors in the migration of CD4+ T cells into the lung is not yet established. To address the 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. The P25 T cells in the Mycobacterium bovis BCG-infected lung and lung-draining mediastinal lymph node expressed chemokine receptors CCR5, CCR6, CXCR3 and CXCR5 which bind chemokines expressed by the BCG-infected lung. To further analyze the role of the chemokine receptors in the migration of the BCG-primed P25 T cells into the lung or mediastinal lymph node, the P25 T cells were adoptively transferred into the BCG-infected wild type mice, and their migration into the lung was monitored. Unexpectedly, blocking of chemokine receptor function with pertussis toxin, a G-protein inhibitor, failed to suppress migration of the T cells into the infected lung although the treatment completely blocked migration of the mediastinal lymph node P25 T cells into the recipient lymph node. The results suggest that interaction of chemokine receptors on mycobacterial antigen-specific Th1 cells with chemokines is dispensable in their migration into the mycobacteria-infected lung.