CD4 T-Lymphocyte Activation in Asthma Is Accompanied by Increased Serum Concentrations of Interleukin-5: Effect of Glucocorticoid Therapy

Abstract

Abstract Peripheral blood mononuclear cells (PBMC) and serum were obtained, on two occasions, from 15 asthmatic patients who required oral glucocorticoid therapy for moderate to severe disease exacerbations. Samples were obtained immediately before commencement of oral glucocorticoids (Day 1) and again after 7 days of treatment (Day 7), when lung function had significantly improved. Samples were also isolated on two occasions 7 days apart from a group of seven untreated volunteers. Expression of CD25, human lymphocyte antigen (HLA-)DR, CD45RA, and CD45RO on CD4 and CD8 T lymphocytes was measured by flow cytometry, and serum concentrations of interleukin-5 (IL-5) were measured using an enzyme-linked immunosorbent assay technique. On Day 1 the asthmatic patients showed significantly higher percentages, as compared with the control subjects of CD4 T lymphocytes expressing the markers CD25, HLA-DR, and CD45RO and significantly lower percentages of CD4 T cells expressing CD45RA. After glucocorticoid therapy, the percentages of CD4 T cells expressing CD25, HLA-DR, and CD45RO were significantly reduced in the asthmatic patients, and the percentages of those expressing CD45RA significantly increased so that by Day 7 expression of all four markers was no longer significantly different from that of the control subjects. By contrast, the percentages of CD8 T cells expressing HLA-DR, CD45RA, and CD45RO in the PBMC of the asthmatic patients on Day 1 were not significantly different from those in control subjects, whereas the percentages of CD25 expressing CD8 T cells were only marginally elevated. Glucocorticoid therapy resulted in no significant change in the expression of all four markers on CD T cells. IL-5 was detectable in the serum of eight of the asthmatic patients on Day 1 (those with the highest peripheral blood eosinophil counts) but in none of these patients on Day 7 after glucocorticoid therapy. Therapy was also associated with a significant fall in the peripheral blood eosinophil counts. Serum IL-5 was undetectable in all the control subjects on both occasions. These observations are consistent with the hypotheses that exacerbations of asthma are associated with activation of “memory” CD4 T lymphocytes secreting IL-5, which regulates eosinophilia, and that glucocorticoid therapy results in reduction of the activation status of these cells concomitant with inhibition of IL-5 secretion.