Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen because it preferentially infects B lymphocytes and consequently activates them to produce immunoglobulins. When cultures of lymphocytes from patients with infectious mononucleosis were stimulated with polyclonal activators, unseparated cells failed to produce immunoglobulins, whereas purified B cells responded normally. Cocultures demonstrated profound suppressor T-cell activity in blood from patients with infectious mononucleosis. Early in this disease, circulating immunoglobulin-secreting cells were elevated, but during the second week their number was strikingly depressed. These data indicate that during infectious mononucleosis, EBV causes polyclonal activation of B cells, reflected by hypergammaglobulinemia and increased circulating immunoglobulin-secreting cells. Next, suppressor T cells become activated and inhibit further B-cell activation. Thus, activation of suppressor T cells in infectious mononucleosis provides a unique additional mechanism of host defense because these T cells inhibit the activation and proliferation of an important target of the causative virus.

The molecular basis for selective interaction among different cells of the immune system is not well understood . Recent work has indicated that specific cell surface carbohydrates may serve as recognition and interaction structures . It has been shown that sugar molecules can provide exquisite specificity to cell surface structures such as blood group determinants (1-3); may be necessary for cell-cell contact required for fertilization (4, 5), differentiation (6, 7), cell aggregation (8, 9), and infection with viruses and bacteria (10, 11); may be involved in the interaction between natural killer cells (12, 13), cytotoxic T cells (14), and suppressor T cells (15) with their targets; and provide receptors required for cell activation by mitogens (16). Elegant studies on the survival of glycoproteins in the circulation have clearly demonstrated that this is dependent upon the nature of the terminal sugar residue on the molecule . For example, it has been shown that uptake of galactose-terminated glycoproteins by hepatocytes involves recognition and binding of the terminal sugar molecules to a lectin-like receptor on the liver cell surface (17). Similar findings were reported for the uptake of Dmannose, N-acetyl-D-glucosamine and L-fucose-terminated glycoproteins by cells of the reticuloendothelial system (18,19) .Sugars have an enormous potential for structural diversity that makes them excellent carriers of biological information. Unlike peptides and oligonucleotides, which depend only on the sequence and number of different monomeric units to encode information, sugar polymers have additional potential diversity because of multiple forms of linkage of the glycosidic units and the possibility of forming branched structures. In this report, we have investigated the nature of signals operating in the interaction between suppressor T cells and their targets and have explored the role of sugars in immunoregulation . We have used T cells obtained from the peripheral blood of patients with acute Epstein-Barr virus (EBV)'-induced infectious mononucleosis (IM) as a source of suppressor T lymphocytes, since during this illness suppressor T cells become activated that profoundly inhibit immunoglobulin (Ig) production in vitro (20,21) . Our results demonstrate that D-mannose and some of its derivatives can significantly reverse suppression by the T cells and suggest an important role for certain sugars as recognition and regulatory signals for the immune system . 'Abbreviations used in this paper: AET, 2-aminoethylisothiouronium bromide; aMM, a-methyl-p-

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Two monocyte-derived cytokines, interleukin-1 (IL-1) and interleukin-6 (IL-6), have been reported to costimulate monocyte-depleted T cell populations in the presence of mitogen, and this effect has been attributed to an accessory function of these molecules. We have now examined further the accessory function potential of IL-1 plus IL-6, and examined how these cytokines promote T cell growth with mitogen. Together, IL-1 and IL-6 additively and, to a small degree, synergistically promote the proliferation of highly purified human peripheral blood T cells with phytohemagglutinin (PHA). However, maximum costimulation by IL-1 plus IL-6 over a wide range of concentrations is significantly smaller than that induced by optimal numbers of monocytes. Also, in contrast to monocytes that costimulate equally effectively T4 positive and T8 positive cells, IL-1 plus IL-6 costimulate T4 positive lymphocytes in marked preference to T8 positive cells. IL-1 plus IL-6 induces IL-2 secretion in T cell cultures costimulated with PHA, and an antibody to the IL-2 receptor, anti-Tac, markedly inhibits PHA-activated T cells costimulated by IL-1 plus IL-6. In addition, IL-1 plus IL-6 enhances the expression of surface IL-2 receptors. Because the costimulatory effect of IL-1 plus IL-6 is quantitatively smaller than that of monocytes, and it is preferentially directed toward T4 positive as opposed to T8 positive T cells, IL-1 plus IL-6, together, appear to represent a selective set of monocyte- derived accessory signals.