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

Abstract

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)