The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo

BACKGROUND The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV). METHODS Mice were infected intranasally with RSV and expression of beta2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c+ CD8+ and CD11c- CD8+ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8+ T cells was assessed by quantitative PCR. RESULTS Following RSV infection CD11c+ CD8+ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 +/- 4.8% of CD8+ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8+ T cells in the absence of RSV infection, its mRNA was expressed in CD8+ T cells of both naïve and RSV infected mice. CD11c+, but not CD11c-, CD8+ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c+ CD8+ T cells were the major subset responsible for IFNgamma production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo. CONCLUSION CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo.