SummaryT cells appear to play a central role in viral bronchiolitis, but the effects of different functional and phenotypic subgroups ofT cells have not been defined. To test the activities ofT cells recognizing individual proteins of respiratory syncytial (RS) virus, virus-specific T cell lines were produced from mice primed by scarification with recombinant vaccinia viruses expressing the major surface glycoprotein (G), fusion protein (F) or second matrix (22K) protein of KS virus. As previously reported, the in vitro characteristics of these cells are predetermined by the choice of KS virus protein: 22K-specific cells are predominantly class I-restricted cytolytic CD8 + cells; F-specific cells, a mixture of cytolytic CD8 + cells and CD4 + cells with a T helper 1 cell (Thl) cytokine secretion profile, whereas those from G-sensitized mice are almost exclusively CD4 + , with Th2 characteristics. Mice infected intranasally with RS virus showed mild illness and recovered fully, but developed respiratory distress after intravenous injections of T cells. Dose-for-dose, infected mice receiving G-specific cells suffered the most severe (sometimes fatal) illness, characterized by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K-specific cells, which alone caused mild shock lung without eosinophilia. F-specific cells caused minimal enhancement of pathology and had little or no effect on the disease caused by G-specific cells. Each cell line reduced lung virus titer and combined injections of G-and 22K-specific cells eliminated infection completely. The in vitro characteristics of these antiviral T cell lines therefore predict the pathological effects in vivo. Moreover, different forms of viral bronchiolitis can be caused by functionally distinct types of activated T cell.

Background and Purpose-Elevated concentrations of the acute-phase reactant C-reactive protein (CRP) predict ischemic cardiac events in both hospital-and population-based studies and may signify a role for inflammation in the destabilization of cardiovascular disease. We examined the relationship between CRP and outcome after acute ischemic stroke. Methods-This was a subgroup analysis from a prospective observational study based in a University Hospital Acute Stroke Unit serving a population of Ϸ260 000. Survival time and cause of death for up to 4 years after the index stroke were determined and related to CRP concentration within 72 hours of stroke and known prognostic variables by a Cox proportional hazards regression model. Results-Ischemic stroke was diagnosed in 228 of 283 consecutive admissions. Median follow-up was 959 days.Geometric mean CRP concentration was 10.1 mg/L. Survival in those with CRP Ͼ10.1 mg/L was significantly worse than in those with CRP Յ10.1 mg/L (Pϭ0.00009, log-rank test). Higher CRP concentration was an independent predictor of mortality (hazard ratio, 1.23 per additional natural log unit; 95% CI, 1.13 to 1.35; Pϭ0.02), together with age and stroke severity on the National Institutes of Health Stroke Scale. Cardiovascular disease accounted for 76% of deaths in those with CRP Ͼ10.1 mg/L and 63% of deaths in those with CRP Յ10.1 mg/L. Conclusions-CRP concentration is an independent predictor of survival after ischemic stroke. These findings are consistent with a role for inflammation in acute ischemic stroke, as well as with the hypothesis that elevated CRP may predict future cardiovascular mortality. (Stroke. 1999;30:981-985.)

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SUMMARYRespiratory syncytial (RS) virus-specific T cell lines were derived from ihe spleens of BALB/c mice primed by intranasal infeclion with RS virus. The lines were expanded by repealed aniigenic stimulation in vitro, and separated into CD4' and CD8 ' T cell-enriched t raciions by immunomagnetie adhesion. The effects of passive Iransfer of these fractions into RS virus infected mice were observed. The most severe immiinopathological changes were seen in mice receiving CD4' cells. Transfer of CD4\ CDS • or both eell fractions caused RS virus-infecied mice to become ill and lose weight. Both eell lines eaused 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. 5x 10' eells were sufficient to decrease lung virus tilre. whereas 2x10'' CDS* cells were needed to produce a similar etfect. The unseparated T cell line and the CD4' cell fraction secreted significantamounlsofIL-3, IL-4 and IL-5 (/*< 0-001). High levels of IL-2 were produced only hy the unseparatedTcell line. The CDS " cell fraction secreted lL-3 only. The results show that, cell-for-cell. CD4' ceils are more anti-viral and more immunopalhogenic than CD8' cells in RS virus infected mice. Such effects may have contributed to the augmented disease seen in some infants vaccinated againsl RS virus. immune responses to RS virus infection. Mice infected wilh RS virus develop a lymphocytic infiltrate in the pulmonary epiihelium. dominated by CDS' T eells at the lime of virus elimination. This occurs before any serological response is detectable, and local epithelial B cells are remarkable by Iheir absence [ 12]. Polyelonal memory T eells can clear persistent RS virus infeetion in immunodefieient miee in the absence of RS virus-specific antibodies (13). as can transfer of CDS' CTL lines or clones-while also eausing haemorrhagic, neuirophilic and sometimes fata! pneumonitis [14]. The role of T helper cells in RS virus-induced imniunopaihology has not been fully examined. Openshaw ei al. [15] found that splenocytes from mice primed inlranasally wilh RS virus exhibited helper T cell memory (demonstrable by virus-specific lL-2 release) whereas those from unprimed mice did not.In order to develop safe and effective vaccines for RS virus, more needs lo be known about the T cell subpopulations involved in protective and harmful responses. Here we describe the in viiro selection, characterization and in rivo effects of cell linesenriched forCD4' andCD8' RS virus-specific Tcells. The CD4+ cells (and to a lesser extent the CDS * cells) redueed lung virus titre and augmented disease in syngcneic mice. 527