CD4+ T cells clear virus but augment disease in mice infected with respiratory syncytial virus. Comparison with the effects of CD8+ T cells

Abstract

SUMMARY Respiratory syncytial (RS) virus-specific T cell lines were derived from the spleens of BALB/c mice primed by intranasal infection with RS virus. The lines were expanded by repealed antigenic stimulation in vitro, and separated into CD4+ and CD8+ T cell-enriched fractions by immunomagnetic adhesion. The effects of passive transfer of these fractions into RS virus infected mice were observed. The most severe immunopathological changes were seen in mice receiving CD4+ cells. Transfer of CD4+, CD8+ or both cell fractions caused RS virus-infected mice to become ill and lose weight. Both cell lines caused an increase in the severity of lung pathology (as monitored by bronchoalveolar lavage) with the appearance or lung haemorrhage and polymorphonuclear cell efflux. In addition, recipients of CD4+ cells developed striking pulmonary eosinophilia. In CD4+ cell recipients. 5×105 cells were sufficient to decrease lung virus titr, whereas 2×106 CD8+ cells were needed to produce a similar effect. The unseparated T cell line and the CD4+ cell fraction secreted significant amounts of IL-3, IL-4 and IL-5 (P < 0·001). High levels of IL-2 were produced only by the unseparated T cell line. The CD8+ cell fraction secreted IL-3 only. The results show that, cell-for-cell CD4+ cells are more anti-viral and more immunopathogenic than CD8+ cells in RS virus infected mice. Such effects may have contributed to the augmented disease seen in some infants vaccinated against RS virus.