The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+T-cells in asthma

CD4+ T-cells are likely to be involved as a source of pro-inflammatory cyto kines in asthma. This study assessed the effects of an infusion of kelixima b (IDEC CE9.1), an anti-CD4+ monoclonal antibody, on peripheral blood CD4T-cells in corticosteroid-dependent asthmatics. Three cohorts of patients (termed C0.5: n=6, C1.5: n=5, and C3.0: n=5) rece ived a single infusion of 0.5, 1.5 or 3.0 mg.kg(-1), respectively, with a f ourth receiving placebo (Cpi: n=6), and were followed-up for 4 weeks. By fl ow cytometry in peripheral blood, pre- and postinfusion assessment was made of. a) CD4 and CD8 counts and mean fluorescence; b) CD25, human leukocyte antigen-DR (HLA-DR), CD45RO and CD45RA expression on CD4+ T-cells; and c) i nterferon (IFN)-gamma, interleukin (IL)-4 and IL-5 expression in CD4+ T-cel ls. Keliximab's in vitro effects on allergen-specific peripheral blood mono nuclear cells (PBMC) proliferation in atopic asthmatics were also evaluated . There was a significant increase in lung function (peak expiratory flow rat e) in the C3.0 group. Following infusion in C0.5, C1.5 and C3.0 but not Cpl : 1) the CD4, but not CD8 count was significantly decreased; 2) there was t otal loss of Leu3a staining; 3) there were significant reductions in the me an fluorescence of OKT4 binding; and 4) there were significant reductions i n the numbers of CD25, HLA-DR, CD45RO and CD45RA/CD4+ cells. There were no changes in CD4+ cell expression of IFN-gamma, IL-4 or IL-5. Keliximab cause d a significant reduction in T-cell proliferation as compared to a control monoclonal antibody. Keliximab, as an anti-CD4 monoclonal antibody, leads to a transient reducti on in the number of CD4+ T-cells and modulation of CD4+ receptor expression in severe asthmatics. The effects of keliximab may be mediated through a d ecrease in CD4+ surface expression and T-lymphocyte numbers, in addition to a reduction in allergen-induced proliferation.