CD56+-T-cell responses to bacterial superantigens and immune recognition of attenuated vaccines.

Natural killer T (NKT) cells, coexpressing natural killer (NK) and T-cell receptors (TCR), are associated with immunity to viruses, tumors, and parasites. A well-characterized subclass of these NKT cells expresses biased TCR and recognizes glycolipids such as alpha-galactoceramide, which is found naturally only in marine sponges and presented by the cell surface glycoprotein CD1d. However, a larger number of T cells present in human blood coexpress the NK marker CD56 and unbiased TCR and do not appear to require CD1 for antigen presentation. Observing high frequencies of CD4 and CD8 coreceptor expression in human CD56+ T cells, we examined the potential role of major histocompatibility complex (MHC) class II molecules in the activation of these cells. Activation of mononuclear cells with bacterial superantigens presented by MHC class II molecules resulted in increased frequency of CD56+ T cells. Primarily, CD4+ cells within the CD56+-T-cell population responded to the bacterial superantigens, and cytokine expression profiles were Th1-like. Further, increased levels of T cells expressing CD56 were observed in mononuclear cell cultures responding to a Staphylococcus aureus vaccine or tetanus toxoid. Collectively, our data suggest that a significant number of CD56+ T cells recognize pathogen-associated ligands in association with MHC class II molecules.