CXC chemokines IP-10 and Mig expression and direct migration of pulmonary CD8+/CXCR3+T cells in the lungs of patients with HIV infection and T-cell alveolitis

The recruitment of cytotoxic T lymphocytes (CTL) is considered to be the ma jor tool for the clearance of HIV from the lower respiratory tract. In this study we evaluated the pathophysiologic role of two lymphotactic CXC chemo kines (IP-10 and Mig) in the lung of HIV-infected patients. These chemokine s stimulate the directional migration of activated T cells and interact wit h a specific receptor (CXC receptor 3, CXCR3). Lymphocytes recovered from t he bronchoalveolar lavage (BAL) of HIV-infected patients with high intensit y T-cell alveolitis were CD8+ T cells expressing high levels of CXCR3 and I FN-gamma, a phenotype that is characteristic of Tc1 cells. Pulmonary T cell s expressing CXCR3 exhibited a high migratory capability in response to IP- 10 and Mig. Alveolar macrophages recovered from patients with T-cell alveol itis bore the IFN-gamma-inducible proteins IP-10 and Mig. A positive correl ation was demonstrated between IP-10, Mig, and IL-15 expression by alveolar macrophages. Interestingly, macrophages isolated from the lung of HIV-infe cted patients with T-cell alveolitis secreted definite levels of CXCR3 liga nds capable of inducing T-cell chemotaxis. Taken together, our data suggest that chemotactic ligands that bind CXCR3 contribute significantly to the a ccumulation of HIV-specific CTL in the lung.