Arthur and Mason

After specific activation by antigen, B cells differentiate into antibody-secreting plasma cells under the influence of a variety of factors (iymphokines) secreted by inducer/helper T cells (1-3). It is not yet clear how many lymphokines are specific for B cells but one, IL-2, has been shown to bind to both activated B cells and activated T cells (4-7), suggesting that at least one lymphokine reacts with both cell types. The role of IL-2 in B cell differentiation is undefined, but it is well established that it plays an essential role in the clonal expansion of T cells (6). The multiplicity of lymphokines raises the question: is there functional specialization among inducer/helper T cells such that some provide differentiation factors reactive solely with B cells while others produce IL-2? Such heterogeneity would, in principle, provide a means of independently regulating the humoral and cellular components of the immune response, and would therefore have important theoretical, and possibly practical, implications. In an earlier publication (8), Woolett et al. showed that an mAb, MRC OX22, raised against PHA-induced rat T cell blasts, and reactive with the high molecular weight forms of the leukocyte-common antigen, revealed a phenotypic heterogeneity among rat CD4 ÷ T cells, in that about two-thirds of these cells reacted with the antibody, and one-third did not. It was further shown (9) that the MRC OX-22subset provided help for B cells in vivo, whereas the MRC OX-22 + population mediated graft-vs.-host reactivity and lethal GVHD. These experiments, although indicating that CD4 + T cells in the rat were functionally heterogeneous, did not provide data as to the ability of the two T cell subsets to secrete the iymphokine IL-2. Herein, using in vitro assays for alloreactivity, IL-2 production, and B cell help, we extend the in vivo data by showing that the MRC OX-22population, while synthesizing little or no IL-2, was very effective at providing help for in vitro antibody production. In contrast, the MRC OX-22 + subset produced as much IL-2 as unfractionated CD4 + T cells, but was relatively ineffective at inducing B cells to differentiate into antibody-secreting cells.