Defective interferon gamma production in neonatal T cells is independent of interleukin-2 receptor binding.
Newborns are more susceptible to fungal, viral, protozoan, and certain bacterial infections than adults. This susceptibility is due in part to a decreased interferon gamma (IF gamma) production. The present investigation focuses on the role of the IL-2 receptor in the deficient IF gamma production in neonatal T cells. IL-2-induced IF gamma production in unstimulated neonatal cord blood and adult peripheral T cells was comparable, but the IF gamma production in CD3-stimulated neonatal T cells was only 20% of the adult production. Neonatal and adult T cells showed no difference in the expression of the 55-kD alpha and 75-kD beta chains of the IL-2 receptor. Blocking of the 55-kD alpha chain of the IL2 receptor with TAC MAb resulted in a marginal reduction in IF gamma release from unstimulated or CD3-stimulated neonatal T cells cultured in the presence of IL-2. In contrast, blocking of the 55-kD alpha chain of the IL-2 receptor in adult T cells caused a 92% and 73% inhibition in IF gamma production in unstimulated and stimulated T cells, respectively. Blocking of the 75-kD beta chain of the IL-2 receptor with TU27 MAb had a marginal effect in both unstimulated and CD3-stimulated neonatal and adult lymphocytes. Binding studies with unstimulated cord blood T cells using [125I]-IL-2 showed a binding affinity that corresponded with the intermediate affinity IL-2 receptor. In CD3-stimulated cord blood T cells, a high-affinity receptor was found.(ABSTRACT TRUNCATED AT 250 WORDS)
von Freeden
U
U
Department of Pediatric Hematology/Oncology, Heinrich-Heine-University Medical Center, Düsseldorf, Germany.
Zessack
N
N
van Valen
F
F
Burdach
S
S
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma