ENHANCEMENT OF HUMAN LYMPHOCYTE PROLIFERATIVE RESPONSE TO PURIFIED PROTEIN DERIVATIVE BY AN ANTI-INTERLEUKIN-2 RECEPTOR A CHAIN ANTIBODY (CD25)

While it is clear that the beta subunit of interleukin-2 receptor (IL- 2R) plays a pivotal role in IL-2-induced signal transduction, the func tion of the alpha subunit, other than modulating the association rate of IL-2, is still unknown. It has been reported that the interaction b etween IL-2 and the IL-2R alpha subunit of several IL-2-dependent muri ne T-cell lines may result in a negative regulatory signal. To confirm this finding, we investigated the effect of an anti-IL-2R alpha antib ody, CD25-8D8, on the proliferative response of human peripheral blood lymphocytes. Lymphocytes from purified protein derivative (PPD)-posit ive donors were cultured with PPD and various concentrations of CD25-8 D8 for up to 9 days, and [H-3]thymidine uptake was measured. Whereas t he proliferative response of human lymphocytes to PPD was suppressed b y high concentrations of CD25-8D8, subinhibitory amounts of CD25-8D8 e nhanced lymphocyte proliferation by 3.5-fold (range 2.2-6.2 fold) on t he second day after maximal [H-3]thymidine uptake had occurred. By its elf, CD25-8D8 could not induce proliferation of washed 5-day PPD-activ ated lymphocytes during reculturing; instead, growth enhancement by CD 25-8D8 was dependent on the presence of PPD-activated culture supernat ant or moderate levels of exogenous IL-2. The enhancing effect of anti -IL-2R alpha antibody, observed in both murine and human systems, rein forces the possibility that binding of IL-2 to the IL-2R alpha chain p lays a negative regulatory role in signal transduction.