Two subsets of human CD4+T helper cells differing in kinetics and capacities to produce interleukin 2 and interferon‐γ can be defined by the Leu‐18 and UCHLl monoclonal antibodies

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Abstract
Human CD4T 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-γ). While the CD4+45R_ subset produced maximal amounts of IL2 within 24 h and IFN-γ within 72 h, the CD4+45R+ subset produced no IL2 within 24 h and merely marginal amounts of IFN-γ 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 UCHLl 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. In contrast, the rate of absorption of IL2 during the first and second day of culture and the expression of IL2 receptors were higher in the CD4+45R− than in the CD4+45R− cell cultures. Despite these findings the CD4+45R− cells consistently showed a stronger proliferative response than the other cell subset. Addition of recombinant IL 2 (rIL 2) did not render the CD4′45R′ cells capable of producing IFN-γ, but small amounts of RIL2 enhanced their proliferative response more efficiently than that of the CD4+45R− cells. Addition of anti-Tac resulted in a reduction of IFN-y production and of DNA synthesis by the CD4+45R− cells. Similarly the DNA synthesis and the small amounts of IFNγ produced by activated CD4+45R− cells were inhibited by anti-Tac.