Acquisition of interleukin-5 secretion by human naive T-helper cells is regulated by distinct signals from both the T-cell receptor/CD3 complex and CD2.
We developed a human naive T-helper (Th) cell differentiation model with anti-CD3 monoclonal antibody (MoAb), using a B-cell line as source of costimulation. In this system, we examined the contribution of the T-cell receptor (TCR)/CD3-derived signals and that of lymphocyte function-associated antigen-1 (LFA-1) and CD2 in regulating Th-cell subset differentiation. We found that lowering the level of anti-CD3 MoAb decreased tumour necrosis factor-alpha (TNF-alpha) production, while increasing secretion of the Th2 cytokines, interleukin-5 (IL-5) and interleukin-13 (IL-13). Secretion of interferon-gamma (IFN-gamma) was not influenced by the strength of the anti-CD3 signal. Under conditions where Th0 cells are generated, co-culture with anti-CD2 F(ab')2 MoAb led to the generation of Th cells that secreted 30-35% less IL-5, while not affecting secretion of IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF). By contrast, anti-CD18 MoAb F(ab')2 inhibited IFN-gamma and GM-CSF levels only in the primary stimulation, but did not affect cytokine levels after restimulation. Neither anti-CD2 nor anti-CD18 F(ab')2 MoAbs could alter cytokine secretion profiles of peripheral blood-derived memory/effector Th cells. Our results indicate that acquisition of IL-5 secretion capability by Th cells is regulated mainly by signals transduced by the TCR/CD3 complex and by the presence of interleukin-4 (IL-4), while the CD2/LFA-3 pathway plays an additional, but minor, role. These regulatory CD2-derived signals, however, are distinct from those generated by the TCR/CD3 complex.
Semnani
R T
RT
Department of Pathology and Committee on Immunology, University of Chicago, IL 60637-1463, USA.
Svoboda
K
K
Khoshnood
B
B
van Seventer
G A
GA
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D018801:CD2 Antigens / Q000494:pharmacology / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007103:Immobilization; D015848:Interleukin-5 / Q000378:metabolism*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D017252:CD3 Complex; D016207:Cytokines; D015848:Interleukin-5; D016169:Lymphocyte Function-Associated Antigen-1; D017260:Receptor-CD3 Complex, Antigen, T-Cell