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.


CONCLUSIONS
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.
Beyer
Marc
M
Department of Respiratory Medicine, NHLI, Imperial College London, Norfolk Place, London, UK. marc.beyer@charite.de
Wang
Hongwei
H
Peters
Nina
N
Doths
Sandra
S
Koerner-Rettberg
Cordula
C
Openshaw
Peter J M
PJ
Schwarze
Jürgen
J
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology*; D018821:CD18 Antigens / Q000276:immunology; D005260:Female; D008168:Lung / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000821:virology*
D039521:CD11c Antigen; D018821:CD18 Antigens