Specific immunotherapy downregulates peripheral blood CD4 and CD8 T-lymphocyte activation in grass pollen-sensitive asthma.

Several lines of evidence indicate that specific immunotherapy may act by modifying the immune responses of T-lymphocytes to the antigen. To evaluate the effect of specific immunotherapy on the activation of T-lymphocytes by cluster of differentiation cells (CD4+ and CD8+) in peripheral blood, the expression of two surface activation markers, the p55 interleukin-2 receptor (CD25) and human leucocyte antigen (HLA)-DR, was studied prospectively on circulating CD4+ and CD8+ T-cell subsets in subjects with grass-pollen sensitive asthma before and after 1 yr of treatment with specific immunotherapy. Twenty five asthmatic patients with pollen sensitivity other than grass, studied out of their pollen season, served as the control group. Specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use during the pollen season of the treatment year. It had a marked effect in reducing the expression of the two activation markers, CD25 and HLA-DR, in both CD4+ (p=0.002 and p=0.005, respectively) and CD8+ (p=0.01 and p=0.01, respectively) T-cell subsets, in parallel with a significant decrease in CD23 expression on B-cells (p=0.008) and in grass-specific immunoglobulin E levels (p=0.01) in the peripheral blood of subjects with grass pollen-sensitive asthma. The decreased T-lymphocyte activation observed in immunotherapy-treated subjects after the treatment year was significant (p=0.05) in comparison with the control group. These data add to the view that the efficacy of specific immunotherapy may be attributed to the downregulation of T-cell responses.

Lymphocyte activation markers in peripheral blood before and after natural exposure to allergen in asthmatic patients.

Activated T cells and their cytokine products are involved in the pathogenesis of asthma. However, little is known about changes in circulating T cell subsets in allergic asthma during natural exposure to allergens. We examined whether natural allergen exposure of patients with atopic asthma is associated, in vivo, with changes of lymphocyte subtypes and activation markers in peripheral blood. Ten patients with atopic mild asthma sensitized only to grass pollen had peripheral venous blood lymphocyte analyses before and during the pollen season. No significant changes were observed. There was an inversion in the CD4/CD8 ratio in the peripheral blood both before (p < 0.05) and during (p < 0.01) seasonal exposure when compared to a group of healthy, age-matched control subjects. Evaluation of T cells expressing CD25 activation marker also demonstrated a significant reduction of CD4+25+ cells and a significant increase of CD+25+ cells compared to the controls. CD23+ cells (B lymphocytes with low affinity Fc IgE receptor) in the asthmatic group out of the pollen season correlated negatively with hyperreactivity to methacholine (p < 0.05). We conclude that in mild allergic asthmatic patients sensitized to grass pollen, blood lymphocyte subsets and their activation markers do not reflect seasonal exposure. Moreover, our findings show that these patients have higher proportions of CD8+ cells expressing higher levels of CD25 in their blood compared to normal subjects both before and during the pollen season.