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

Ann Allergy Asthma Immunol. 2003 Jul;91(1):65-70. doi: 10.1016/S1081-1206(10)62061-3.


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 gamma-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.

MeSH terms

  • Adolescent
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • CD3 Complex / immunology*
  • Child
  • Child, Preschool
  • Common Variable Immunodeficiency / blood
  • Common Variable Immunodeficiency / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-15 / immunology
  • Interleukin-15 / pharmacology*
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • fas Receptor / immunology


  • Antigens, CD
  • CD3 Complex
  • Interleukin-15
  • Interleukin-2
  • fas Receptor