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 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.


CONCLUSIONS
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.
Lin
Syh-Jae
SJ
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan, ROC. sjlino@adm.cgmh.org.tw
Chao
Hsun-Chin
HC
Chang
Kwei-Wen
KW
Yan
Dah-Chin
DC
D000293:Adolescent; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
D015703:Antigens, CD; D017252:CD3 Complex; D019409:Interleukin-15; D007376:Interleukin-2; D019014:fas Receptor