Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones.
The effects exerted on the in vitro development of purified protein derivative (PPD)-specific or Dermatophagoides pteronyssinus group I (Der p I)-specific T cell lines (TCL) and T cell clones (TCC) by IL-4 or IFN-gamma addition or neutralization in human PBMC cultures were examined. PBMC from two normal individuals, which were stimulated with PPD and then cultured in IL-2 alone, developed into PPD-specific TCL and TCC able to produce IFN-gamma and IL-2 but not IL-4 and IL-5 (Th1-like). IFN-gamma or anti-IL-4 antibody addition in bulk cultures before cloning did not influence the PPD-specific TCL profile of cytokine production. In contrast, the addition of IL-4 resulted in the development of PPD-specific TCL and TCC able to produce not only IFN-gamma and IL-2 but also IL-4 and IL-5. PBMC from one atopic Der p I-sensitive patient, which were stimulated with Der p I and then cultured in IL-2 alone, developed into Der p I-specific TCL and TCC able to produce IL-5 and large amounts of IL-4 but no IFN-gamma (Th2-like). The addition in bulk cultures, before cloning, of either IFN-gamma or anti-IL-4 antibody markedly inhibited the development of Der p I-specific T cells into IL-4- and IL-5-producing TCL. Accordingly, the development into Der p I-specific Th2-like TCC was significantly reduced by the addition of IFN-gamma in bulk culture and was virtually suppressed by the presence of both IFN-gamma and anti-IL-4 antibody. These data suggest that the presence or the absence of IL-4 and IFN-gamma in bulk cultures of PBMC before cloning may have strong regulatory effects on the in vitro development of human CD4+ T cells into Th1 or Th2 clones.
Maggi
E
E
Division of Clinical Immunology and Allergology, University of Florence, Italy.
Parronchi
P
P
Manetti
R
R
Simonelli
C
C
Piccinni
M P
MP
Rugiu
F S
FS
De Carli
M
M
Ricci
M
M
Romagnani
S
S
D000328:Adult; D002478:Cells, Cultured; D002999:Clone Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014373:Tuberculin / Q000276:immunology
D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate