CXCR3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allografts and mediate chemotaxis of T cells at sites of rejection

The attraction of T lymphocytes into the pulmonary parenchyma represents an essential step in mechanisms ultimately leading to lung allograft rejectio n. In this study we evaluated whether IP-10 (CXCL10), a chemokine that is i nduced by interferon-gamma and stimulates the directional migration of acti vated T cells, plays a role in regulating the trafficking of effector T cel ls during lung allograft rejection episodes. Immunohistochemical examinatio n showed that areas characterized by acute cellular rejection (grades 1 to 4) and active obliterative bronchiolitis (chronic rejection, Ca) were infil trated by T cells expressing CXCR3, ie, the specific receptor for CXCL10, I n parallel, T cells accumulating in the bronchoalveolar lavage of lung tran splant recipients with rejection episodes were CXCR3+ and exhibited a stron g in vitro migratory capability in response to CXCL10, In lung biopsies, CX CL10 was abundantly expressed by graft-infiltrating macrophages and occasio nally by epithelial cells. Alveolar macrophages ex-pressed and secreted def inite levels of CXCL10 capable of inducing chemotaxis of the CXCR3+ T-cell line 300-19; the secretory capability of alveolar macrophages was upregulat ed by preincubation with interferon-gamma. Interestingly, striking levels o f CXCR3 ligands could be demonstrated in the fluid component of the broncho alveolar lavage in individuals with rejection episodes. These data indicate the role of the CXCR3/CXCL10 interactions in the recruitment of lymphocyte s at sites of lung rejection and provide a rationale for the use of agents that block the CXCR3/CXCL10 axis in the treatment of lung allograft rejecti on.