Immune mechanisms in congenital cytomegalovirus infection: activation of CMV-specific T helper cells (CMV-Th) by exogenous IL-2.
Infants with congenital CMV infection have a specific defect in CMV-induced lymphocyte proliferation, providing a model for investigation of mechanisms of viral immune recognition and immune response. In the present study the possible role of a defect in lymphokine activation of CMV-specific T helper cells (Th) was examined. IL-1 activity was detected in supernatants of patient mononuclear cell (MNC) cultures stimulated with CMV. In contrast, no IL-2 activity could be detected in supernatants of CMV-stimulated MNC cultures, whereas PHA induced normal IL-2 production. Addition of low concentrations of either crude TCGF or recombinant IL-2 (rIL-2) resulted in 2-4 fold augmentation of CMV-specific lymphocyte proliferation; exogenous IL-2 had no effect on MNC responses to HSV. CMV-specific Th lines/clones were established from three congenital CMV patients by initial stimulation of MNCs with CMV antigen and 0.1 U/ml rIL-2, followed by repeated stimulation with CMV, HLA-matched allogeneic feeder cells and 10% TCGF. The resulting CMV Th lines/clones proliferated specifically in response to stimulation with CMV antigen and produced endogenous IL-2. Thus, the immune deficiency associated with congenital CMV may either be due to an intrinsic defect in CMV-Th activation or CMV-specific suppressor cell activity.
Gehrz
R C
RC
Sutton Immunobiology Research Laboratory, Children's Hospital of St. Paul, Minnesota 55102.
Peterson
E S
ES
Liu
Y N
YN
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000276:immunology; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008938:Mitosis / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000956:Antigens, Viral; D007375:Interleukin-1; D007376:Interleukin-2