Up-regulation of VCAM-1 and differential expansion of β integrin-expressing T lymphocytes are associated with immunity to pulmonary Mycobacterium tuberculosis infection

Immune responses rely on an intricate system of adhesion molecules to coordinate the homing and retention of lymphocytes in both secondary lymphoid tissues and at sites of infection. To define the events associated with pulmonary immune responses, the expression of endothelial addressins and integrins on T cells was analyzed during Mycobacterium tuberculosis infection. In infected lung, expression of endothelial VCAM-1, but not mucosal addressin cell adhesion molecule-1, was up-regulated from 4 wk postinfection and persisted to at least 12 wk. Subsequent analysis of the corresponding integrins expressed on lung CD4(+) and CD8(+) T cells revealed an accumulation of beta(1)(high)/beta(7)(-/low), and to a lesser extent beta(7)(high), integrin expressing T cells during infection. Examination of integrin heterodimers showed that while alpha(4) integrin was predominantly expressed on beta(1)(high)/beta(7)(-/low) cells, alpha(E) integrin was primarily associated with beta(7)(high). The majority of activated/memory T cells recruited during infection expressed high levels of beta(1) integrin and undetectable or low levels of beta(7) integrin. These T cells were capable of producing IFN-gamma, a cytokine crucial for controlling M. tuberculosis infection. Rapid expansion of beta(1)(high), beta(7)(-), and beta(7)(high) T cell populations in the lung upon secondary mycobacterial infection indicates the participation of these populations in the acquired immune response to the infection. Furthermore, treatment of infected mice with mAb to alpha(4) or alpha(4)beta(7) integrin led to a reduction in lymphocytes and increase in granulocytes in the pulmonary infiltrate. These results reveal a crucial role for adhesion molecules in the generation of an effective pulmonary immune response to M. tuberculosis infection.