Two subsets of human CD4+ T helper cells differing in kinetics and capacities to produce interleukin 2 and interferon-gamma can be defined by the Leu-18 and UCHL1 monoclonal antibodies.
Human CD4+ T helper cells were separated into CD4+45R+ and CD4+45R- cells. When stimulated with the polyclonal activator staphylococcal enterotoxin A in the presence of autologous monocytes, these two subsets exhibited a striking difference in production of interleukin 2 (IL2) and interferon-gamma (IFN-gamma). While the CD4+45R- subset produced maximal amounts of IL2 within 24 h and IFN-gamma within 72 h, the CD4+45R+ subset produced no IL2 within 24 h and merely marginal amounts of IFN-gamma as assayed after 24 to 96 h. This discrepancy between the subsets was found when the cells were stimulated by other accessory cell-dependent activators and by the accessory-independent combination of the calcium ionophore A23187 and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate as well. The inability of the CD4+45R+ cells to produce IL2 during the first day of culture was not due to any modulation of either the CD4 or the CD45R antigens, as purified CD4+45R+ cells obtained by negative panning selection with the reciprocal UCHL1 monoclonal antibody responded in a similar manner as the positively selected sorted CD4+45R+ cells. Analysis of the kinetics of IL2 production by the two T helper cell subsets clearly demonstrated that the IL2 recorded after 1 day of culture was entirely produced by the CD4+45R- cells, whereas the CD4+45R+ cells produced IL2 during and after the second day of culture. This discrepancy in kinetics was not due to an increased absorption of IL2 by the CD4+45R+ cells during the first day of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Dohlsten
M
M
Department of Tumour Immunology, University of Lund, Sweden.
Hedlund
G
G
Sjögren
H O
HO
Carlsson
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007700:Kinetics; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens