Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects.
The cytokine secretion profiles of T cell lines (TCL) specific for purified protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great majority of PPD-specific TCC derived from nonatopic individuals did not produce IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic individuals are able to produce IL-4 and IL-5 in response to bacterial antigens, such as PPD and SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.
Division of Clinical Immunology and Allergology, University of Florence, Italy.
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Parronchi
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De Carli
R
R
Manetti
C
C
Simonelli
M P
MP
Piccinni
D
D
Macchia
E
E
Maggi
G
G
Del Prete
M
M
Ricci
S
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Romagnani
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002999:Clone Cells; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013300:Streptokinase; D013755:Tetradecanoylphorbol Acetate; D014373:Tuberculin
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D015848:Interleukin-5; D011948:Receptors, Antigen, T-Cell; D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma; D013300:Streptokinase; D013755:Tetradecanoylphorbol Acetate