IL-4 (B cell-stimulatory factor 1) regulates multiple aspects of influenza virus-specific cell-mediated immunity.
The effect of endogenous and exogenous IL-4 on the generation of influenza virus-specific cell-mediated immunity was examined. When added at the onset of the culture, IL-4 augmented both cluster of differentiation (CD)8+ lymphoproliferation and MHC-restricted, influenza virus-specific cytotoxicity. When added 5 or 6 days after initiation of cultures, IL-4 was highly effective at augmenting cytotoxicity, whereas no augmentation of proliferation was observed. This disassociation of the effect of IL-4 on lymphoproliferation and cytotoxicity indicated that IL-4 was providing a late signal in CTL generation. Studied at the level of CTL precursor maturation in microcultures, IL-4 was found not to increase cytotoxicity but to be required, in some cases, for the generation of cytotoxicity. Endogenous IL-4 production was observed and demonstrated to be important because neutralizing antiserum to IL-4 suppressed CTL development. In contrast to the effects of IL-4 when added later to the cultures, pulsing the lymphocytes with IL-4 before, or shortly after, exposure to antigen resulted in suppression of the CTL response. These results indicate that IL-4 has differentiative, proliferative, and suppressive effects on cell-mediated immune responses.
Horohov
D W
DW
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Crim
J A
JA
Smith
P L
PL
Siegel
J P
JP
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D000956:Antigens, Viral / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D009980:Influenza A virus / Q000276:immunology*; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D000939:Epitopes; D007378:Interleukins; D015847:Interleukin-4