Mls presentation by peritoneal cavity B cells.

DBA/2J spleen and peritoneal cells were compared for their ability to present the minor lymphocyte stimulatory superantigen Mls-1a. Although capable of Mls presentation in vivo, peritoneal cells were less effective than spleen cells in vitro. This difference was not due to cell concentration or culture duration. Flow cytometric comparison of spleen and peritoneal B cells revealed no significant differences in cell surface markers needed for cognate interaction with T cells. Resolution of peritoneal B cell subsets by cell sorting revealed that even though B-1 cells were capable of Mls presentation, they were less effective than B-2 cells. Mixing experiments showed that B-1 cells did not inhibit B-2 cell presentation of Mls. In contrast, total peritoneal cells inhibited T cell responses to Mls presented by spleen cells. The peritoneal cavity harbors B cells that can present Mls as well as other cells that can suppress this response.

Functional modulation of activated lymphocytes by time-varying magnetic fields.

Time-varying magnetic fields (TVMF), especially those of extremely low frequency (below 250 Hz), have been reported to have profound effects on biological systems due to the induced currents since the biological systems consist of electrolyte solution. We have been interested in utilizing TVMF for cellular immunomodulations, and have shown that the TVMF could augment macrophage activation. In this study, the effect of TVMF on lymphocyte activation was studied. Murine spleen lymphocytes were isolated from DDY mice and incubated in the presence of Concanavalin A (ConA) for 72 h. The lymphocytes were exposed to TVMF for various durations, from 20 min to 2 h. The proliferation activities of lymphocytes were assayed by ELISA by use of 5-bromo-2'-deoxy-uridine Labeling and Detection Kit III (Roche Diagnostic Corp. Indianapolis, IN, USA). The IL1beta and IL2 concentrations in the culture medium were measured by ELISA assay. The IL2 receptor expression on the lymphocytes was evaluated by FACS analysis by use of FITC-conjugated monoclonal antibody. The proliferation activities were significantly enhanced by the TVMF for up to 40 min exposure from the initiation of ConA stimulation. The degree of augmentation effects, defined by the ratio of activation index of with and without TVMF, was varied from 1.1 to 2.7, and related to the lymphocyte responsiveness to the ConA. The less responsive cells showed more TVMF augmentation effects. The TVMF exposure after 40 min from ConA addition showed no effect, suggesting that the TVMF effects are most likely related to the Ca ion influx. The prolonged exposure of TVMF depressed the augmentation effects, which was caused by the depressed IL-2 receptor expression although both IL1-beta and IL-2 productions were not affected.

Direct binding of the Mtv7 superantigen (Mls-1) to soluble MHC class II molecules.

The superantigen encoded by the mouse mammary tumor virus (MMTV) is a potent stimulator of T cells when bound to MHC class II molecules. Recent data from this laboratory have shown that the Mtv7 superantigen, Mls-1, elicits a strong T cell response when presented by HLA-DR. To expand these observations further, we have produced the 28 kDa extracellular domain and the 18 kDa carboxy-terminal subfragment of the Mls-1 protein in E. coli and studied their interaction with human MHC class II molecules in vitro. In this report, we demonstrate direct binding of these recombinant forms of the Mls-1 protein to soluble HLA-DR1 and HLA-DR4, but not to HLA-A2. Our data imply a unique class II interaction site of retroviral superantigens that is not shared with bacterial superantigens.

Mouse intestinal epithelial cells express the self superantigen Mls1a.

In previous studies, we demonstrated that intestinal epithelial cells of the mouse small intestine could present exogenous antigen to specific CD4+ T cell hybridomas. We now report on the ability of normal enterocytes to present the self superantigen Mls1a. Enterocytes from Mls1a but not from Mls1b strains stimulated interleukin-2 production through a V beta 6+ T cell hybridoma specific for Mls1a determinants. Antibody inhibition experiments showed that enterocytes presented Mls determinants via a major histocompatibility complex class II-dependent mechanism. Furthermore, the ability of enterocytes to activate V beta 6+ Mls1a-specific T cells was inhibited by monoclonal antibodies against the Orf protein encoded by an Mtv-7 provirus which is associated with Mls1a expression. These findings provide evidence for the first time that Mls determinants are expressed on normal enterocytes and support the theory of a possible role of these cells in extrathymic selection of T cell receptor V beta repertoire of intraepithelial T lymphocytes.

Lectins and superantigens: membrane interactions of these compounds with T lymphocytes affect immune responses.

1. Lectins and superantigens belong to two different families of macromolecules which are able to interact with cells of the immune system. 2. The principal mechanisms by which they modulate immune responses are presented in this review. 3. Possible similarities shared by these proteins and their common mechanisms of action upon immunocytes will be presented along with a brief discussion regarding the role of these molecules in physiological immune responses and human diseases.