Unique pattern of interleukin 2 receptor expression by lymphocytes in response to anti-Leu 4 monoclonal antibody: relationship to monocyte accessory cell function.

Abstract

The relationship of early interleukin 2 receptor (IL2R) expression to subsequent DNA synthesis by mitogen-stimulated human mononuclear cells (MC) was studied. For serial dilutions of a given mitogen, the percentage of lymphocytes expressing IL2R after 1 day of culture was plotted vs 3H-thymidine incorporation on day 3, and the IL2R value associated with a proliferative response of 50,000 counts per minute (IL2R-50K) determined. A mean IL2R-50K value of 7 characterized PHA, Con A, and OKT3 responses, while a higher mean value of 29 characterized anti-Leu 4(L4) responses. As tested in OKT3 and L4 systems, the addition of exogenous IL2 did not alter IL2R-50K values. Because both OKT3 and L4 recognize the lymphocyte CD3 antigen but react with different monocyte Fc receptors, the role of monocytes in producing elevated L4 IL2R-50K values was explored. MC from healthy L4 nonresponders (NR), induced to proliferate with L4 in the presence of responder (R) monocytes, also yielded an elevated mean IL2R-50K value of 31. In contrast, direct stimulation of R-MC, NR-MC, or NR-MC plus R monocytes by L4-coated sepharose beads produced lower mean IL2R-50K values of 12 or 13. Two-color cytofluorescence studies measuring IL2R and transferrin receptor (TR) on day 2 of culture revealed that most of the increase in IL2R+ cells in response to L4 was attributable to IL2R+TR-cells. These findings suggest that crosslinking of lymphocyte-bound soluble L4 by R monocytes leads to a uniquely elevated pattern of IL2R expression involving a disproportionate increase in the level of IL2R+TR-cells.