Regulation of freshly isolated, IL-4-producing T cells: IFN-gamma-sensitive and -resistant cells.
Cytokine responsiveness of interleukin-4 (IL-4)-producing T cells (IL-4p) during primary in vitro stimulation was investigated. Freshly isolated T cells were stimulated with anti-CD3 epsilon antibodies in the presence of macrophages. Using limiting dilution analysis, we found that IL-4p were not detected when endogenous IL-2 activity was blocked with anti-IL-2 antibodies. These data support previous observations that IL-4p require IL-2 for induction, and further indicate the presence of macrophages was not sufficient to overcome the requirement for IL-2. The effects of IFN-gamma on IL-4p were studied in this system. Addition of exogenous IFN-gamma decreased the frequency of IL-4p but did not completely inhibit induction of these cells. Furthermore, blocking endogenous IFN-gamma during stimulation resulted in a 2- to 4-fold increase in the frequency of IL-4p detected. These data demonstrate the novel finding that both IFN-gamma-resistant and IFN-gamma-sensitive IL-4p were present in freshly isolated T cell populations. Thus, during early in vitro culture, there were at least two types of IL-4p, both of which require IL-2. These data indirectly support a current model of Th ontogeny as defined by cytokine production patterns, and extend the model to include cytokine responsiveness.
Naujokas
M F
MF
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
Schmitt
E
E
Finnegan
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma