A kinetic comparative study on lymphocyte responses to superantigen and phytohemagglutinin: reciprocal presentation of superantigen on the surface of activated lymphocytes.

The kinetics of thymidine incorporation into fractionated T lymphocytes responding to bacterial superantigens were compared to those of cells activated by phytohemagglutinin (PHA). Evident differences between the kinetics of cell proliferation induced by PHA-P and staphylococcal enterotoxin B (SEB) emerged after Day 4 of culture. PHA-P-induced proliferative responses of peripheral blood mononuclear cells (PBMCs) and fractionated cells were apparent on Day 4 because of the presence of accessory cells in the initial cell suspensions. This gradually diminished in correlation with the decline of accessory cells in the cultures. The SEB-induced cell growth (PBMCs and CD4+ cells), however, continued until Day 9 of the culture. This finding suggests the reciprocal usage of MHC class II molecules to present SEB by activated T lymphocytes for superantigen-induced T cell activation and suggests that superantigen-related immune activation may depend in part on the potential of activated T lymphocytes to mediate reciprocal cell-to-cell interactions in the presence of superantigens. The decline observed in the CD8+ cell response to SEB and toxic shock syndrome toxin-1 after Day 4 was revived by exogenous recombinant interleukin-2 (rIL-2) supplementation, suggesting that the consequent autocrine or paracrine secretion of IL-2 from the responding cells is essential for subsequent cell proliferation. SEB-induced cell proliferation was significantly suppressed by anti-CD11a (lymphocyte function-associated antigen-1; LFA-1, alpha-chain) monoclonal antibody, and the inhibitory effect was most obvious in 6-day cultured CD8+ lymphocytes. The results suggest that the lymphocyte response associated with the cell-to-cell copresentation of superantigens involves LFA-1 molecules as an accessory factor, particularly in CD8+ lymphocytes.