The beta2 integrin CDIIc 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 beta 2 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 naive 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 IFN gamma 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.