Effect of interleukin 15 and interleukin 2 on anti-CD3-induced T-cell activation and apoptosis in children with common variable immunodeficiency

Background: Defective T-cell function and susceptibility to apoptosis following activation may contribute to the immunodeficiency observed in common variable immunodeficiency (CVID) patients. Interleukin (IL) 2 benefits CVID children by boosting T-cell function. Objective: To investigate the effect of another IL-2 common γ-chain signaling cytokine, IL-15, on T-cell activation and apoptosis of peripheral blood mononuclear cells (PBMCs) from children with CVID compared with IL-2. Methods: Five children treated at the Chang Gung Children's Hospital, Taoyuan, Taiwan, during 1998 to 2002 who fulfilled World Health Organization criteria for CVID and 8 age-matched, healthy controls were enrolled. The PBMCs were stimulated with anti-CD3 in the presence or absence of IL-2 and IL-15 for 4 days, followed by 24-hour incubation with anti-Fas to induce apoptosis. Surface expression of CD69, CD25, and CD95 (Fas) on CD3⁺ T cells was evaluated by flow cytometry. The degree of apoptosis was evaluated by propidium iodide-phycoerythrin/annexin V-fluorescein isothiocyanate flow cytometric staining. Results: Following anti-CD3 activation, CD69 and CD25 expression of CVID CD3⁺ PBMCs was enhanced to levels comparable to controls. Exogenous IL-15 resulted in further enhancement of anti-CD3-induced CD69 expression to a greater extent than that achieved with IL-2. A greater degree of apoptosis was found in CVID patients than controls following anti-CD3 stimulation (P = 0.001). IL-15 but not IL-2 further increased anti-CD3-induced apoptosis in control PBMCs (P = 0.001). In contrast, the degree of anti-CD3-induced apoptosis in CVID PBMCs was unaffected by IL-15 or IL-2. Addition of anti-Fas to cultures prestimulated with anti-CD3 further increased the apoptosis in control PBMCs but had no effect on apoptosis of CVID PBMCs. Conclusion: Comparable anti-CD3-induced activation and enhanced apoptosis were observed in PBMCs from children with CVID compared with controls, The degree of apoptosis in CVID PBMCs was not affected by exogenous IL-15 or anti-Fas, suggesting a preactivated status in vivo.