No abstract

The production of several lymphokines by freshly isolated CD4+ T cells has been analyzed at the single-cell level, after stimulation with staphylococcal enterotoxin B (SEB). High frequencies of cells producing interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were induced, but very low frequencies of CD4+ T cells produced IL-4, IL-5 or IL-10 in response to SEB. Exogenously added IL-4 markedly altered the lymphokine profile induced during primary SEB stimulation. IFN-gamma production was reduced, while a high fraction of cells contained IL-10 and IL-4 after activation in the presence of IL-4. We further demonstrate that IL-4 and IL-10 or IFN-gamma production was selectively induced in resting, high-density CD4+ T cells during primary stimulation, by SEB + IL-4 or SEB. Under conditions where both IL-10 and IFN-gamma were produced, most cells contained only one of the two lymphokines.

We do not agree with the analysis of Langman and Cohn on the function of Ig receptors. We have reviewed the available literature regarding anti-Ig activation of B cells and found it contradictory and unconvincing. We have presented experimental evidence on the inability of Ig receptors on B cells to mediate activation or tolerogenic signals. We suggest that the Ig receptors serve to focus antigen to specific B cells so the B cells can be activated by TI antigens or helper T cells. The Ig molecules also bind foreign antigen and thereby initiate internalization and antigen processing. The processed peptides are exported to the membrane, where they associate with MHC class II antigens, thus transforming B cells into efficient antigen-presenting cells.

Human and mouse immunoglobulins (Ig) or F(ab')2 fragments of rabbit Ig were conjugated to lipids and the conjugates inserted into the membrane of mouse spleen cells. It was found that nearly all B cells, but not T cells, became decorated with lipid immunoglobulin. Both endogenous Ig receptors and inserted Ig capped after the addition of cross-linking F(ab')2 antibodies and in both cases capping required energy. Capping of endogenous mouse Ig led to co-capping of inserted human Ig, but the reverse was not true.

Purified CD8+ T cells were recently shown to produce TH1 as well as TH2 types of cytokines upon restimulation, indicating an important role for these cells in regulation of immune responses. However, it is not known if the CD8+ cells would contribute to cytokine production in the presence of cytokine secreting CD4+ cells. In the present study the authors have investigated the proportion of cytokine-producing CD4+ and CD8+ cells in the spleen after in vitro or in vivo stimulation. They found that stimulation of spleen cells with the superantigen Staphylococcal Enterotoxin B (SEB) in the presence of IL4 promoted production of IL10 and IFN gamma predominately by CD8+ cells. In contrast, the production of IL4 was almost exclusively confined to the CD4+ subset. When priming with SEB in vivo before subsequent restimulation in vitro, a protocol previously shown to induce anergy, up to 80% of the IL10 and IFN gamma positive cell expressed the CD8 marker. Taken together, these results emphasize the important role of cytokine-producing CD8+ cells and indicate that CD4+ and CD8+ T cells may, in a given situation, produce distinct cytokines.