CD4 T-Lymphocyte Activation in Acute Severe Asthma: Relationship to Disease Severity and Atopic Status

Abstract

Abstract Lymphocytes are prominent among the inflammatory cells infiltrating the asthmatic airways, and several studies have suggested that cell-mediated immunity may play a role in the pathogenesis of chronic asthma. We have measured (1) the expression of activation markers on the CD4+ and CD8+ T-lymphocyte phenotypic subsets in the peripheral blood of patients hospitalized with acute severe asthma (“status asthmaticus”), and (2) the serum concentrations of two proteins elaborated by activated T-lymphocytes (interferon-γ and the soluble interleukin-2 receptor). The results were compared with those in control subjects (mild asthma, chronic obstructive airway disease, and normal). CD4+ lymphocytes from patients with acute severe asthma showed significant increases in the expression of three surface proteins associated with lymphocyte activation (interleukin-2 receptor [IL-2R], class II histocompatibility antigen [HLA-DR], and “very late activation” antigen [VLA-1]) as compared with those from normal control subjects. In contrast, CD8 cells were devoid of IL-2R and VLA-1, in both patients with acute severe asthma and control subjects, and the expression of HLA-DR on these cells was not increased above that of control subjects. The serum concentrations of interferon-γ and soluble IL-2R were significantly elevated in patients with acute severe asthma as compared with all the control groups. Concentrations decreased as the patients improved clinically during the first 3-day period of hospital treatment. At 3 days after admission, a significant correlation was observed between the improvement in airway obstruction as measured by the change in the peak expiratory flow rate and (1) the decrease in the percentages of peripheral blood CD4 T-lymphocytes expressing IL-2R, and (2) the decrease in the serum concentrations of soluble IL-2R. Atopic patients with acute severe asthma had significantly fewer numbers of peripheral-blood-activated CD4 T-cells on admission than did nonatopic patients, and they also tended to have lower or normal serum concentrations of soluble T-cell mediators, suggesting that additional factors may have been contributing to the acute bronchoconstriction observed in these patients. These observations provide further evidence that CD4 T-lymphocyte activation is important in the pathogenesis of acute severe asthma.