Functional heterogeneity of CD4+ T lymphocytes: two subpopulations with counteracting immunoregulatory functions identified with the monoclonal antibodies WR16 and WR19.

Monoclonal antibodies (MoAbs) WR16 and WR19 bound to 47% and 43% of CD4+ tonsil T lymphocytes, respectively. WR16 immunoprecipitated a 220,000 molecular weight (MW) component that was also expressed on CD8+ lymphocytes and on B lymphocytes, whereas binding of WR19 was restricted to CD4+ lymphocytes. Binding of these two MoAbs on freshly prepared tonsil CD4+ T lymphocytes was mutually exclusive, and they were used to prepare reciprocal CD4+ subpopulations by negative depletion using the panning technique. Recombination of subsets isolated in this way with autologous B lymphocytes activated with pokeweed mitogen demonstrated that WR16+/OKT4+ lymphocytes suppressed B lymphocyte Ig secretion, whereas WR19+/OKT4+ lymphocytes helped B lymphocyte Ig secretion. Removal of WR16+ cells from a CD4+ helper cell population enhanced B lymphocyte Ig secretion rate, whilst the re-addition of WR16+ cells to WR19+ helper cells reduced B lymphocyte Ig secretion rates to that seen with non-fractionated CD4+ helper cells. The overall level of helper activity induced by a given CD4+ population was thus a consequence of an interaction between WR19+ helper cells and WR16+ suppressor cells. The WR16+ subset of CD4+ cells exhibited a greater proliferation rate than WR19+/CD4+ cells in response to mitogen. Proliferation of negatively selected WR16+/CD4+ lymphocytes was inhibited by pretreatment with WR16, which also induced a concomitant increase in the level of suppressor activity of these cells. Expression of the antigens identified by these two MoAbs was not constant as phytohaemagglutinin activation of T lymphocytes induced a loss of WR16 binding with a simultaneous increase in the level of WR19 bound/cell and in the proportion of WR19+ cells. T lymphocyte clones selected from a normal population were composed of a disproportionately high number positive for WR19 and negative for WR16. These data indicated that the absence of the WR19 antigen on WR16+ cells may be transient as the antigen was acquired by the majority of CD4+ T lymphocytes after activation. These two MoAbs may therefore be used to predict the functional status of a heterogeneous population of CD4+ lymphocytes and may also prove to be of use in the study of CD4+ T lymphocyte activation.