Abstract
BackgroundThe 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).MethodsMice were infected intranasally with RSV and expression of β2 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.ResultsFollowing 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 IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo.ConclusionCD11c 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.
Highlights
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
Respiratory Research 2005, 6:70 http://respiratory-research.com/content/6/1/70 to be confined to cells of myeloid origin and these molecules have been used as markers to define certain cell populations, e.g. CD11b for macrophages [2] and CD11c for dendritic cells [3]. β2 integrins are of critical importance for the development of functional immune responses; a mutation in the CD18 gene, resulting in decreased expression of β2 integrins and in defective migration of granulocytes, causes an immune defect termed leukocyteadhesion deficiency [1]
respiratory syncytial virus (RSV) infection results in increases in numbers of CD11c+ CD8+ T cells in the lung Recently, we have reported a population of CD8+CD11c+ T cells in the lung ten days after RSV infection [14]
Summary
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. The studies regarding β2 integrins on T cells were mostly conducted in mouse-models of infection with LCMV, a virus that induces systemic immune responses involving many different organs [12]. We hypothesized that CD11c is a marker of antigen-specific cytotoxic T cells, which is expressed following activation, rather than being transferred from APC during cell-cell interactions. Such a transfer from APC to T cells has been described for the co-stimulatory molecule CD80 [13]. We sought to define a function of CD11c when expressed on T cells following RSV infection
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