Human T lymphocyte mitogenesis in response to the B oligomer of pertussis toxin is associated with an early elevation in cytosolic calcium concentrations

Abstract

Pertussis toxin was found to serve as a mitogen in the human T lymphocyte, an effect which could be mimicked by its resolved binding component, the B oligomer. The mechanism of action of this component appeared to involve a rapid and sustained elevation of cytosolic calcium levels, as monitored by fura-fluorescence. The source of mobilized calcium was predominantly extracellular, suggesting that the binding of the B oligomer to the T cell plasma membrane in some way elicited calcium channel activation. Notably, the influx of calcium was not observed with cholera toxin, an AB toxin lacking mitogenic effects on the human T lymphocyte.

Antibody-Mediated Neutralization of Pertussis Toxin-Induced Mitogenicity of Human Peripheral Blood Mononuclear Cells

“…A decrease in mitogenicity was observed at high serum concentrations. Similar experiments using the purified B-pentamer of pertussis toxin yielded the same results (data not shown), consistent with previous reports that B-pentamer alone induces PBMC proliferation (32,33). Whole toxin was used for all subsequent assays in order to assess antibodies to the S1 subunit that may affect B-pentamer activity.…”

“…However, the B-pentamer of pertussis toxin has been shown to have activity in addition to its role in facilitating entry of S1 into the cytoplasm of the target cell. The B-pentamer is mitogenic for human T cells and murine splenocytes (32,33), induces oxidation of glucose in rat adipocytes (33), alters macrophage adhesion (38), and mimics the effects of selectins on the regulation of leukocyte trafficking (24). A recent report showed that an S3-S4 dimer was as strongly mitogenic as the B-pentamer, and in vitro stimulation of naive lymphocytes by the S3-S4 dimer resulted in reversal of the normal CD4 ϩ / CD8 ϩ T-cell ratio (12).…”

Mechanisms of pertussis toxin‐induced myelomonocytic cell adhesion: role of Mac‐1(CD11b/CD18) and urokinase receptor (CD87)

“…and inositol trisphosphate (IP 3 ) levels, and an increase in tyrosine phosphorylation of certain cellular proteins. [4][5][6][7] Moreover, PTX rapidly promotes human platelet aggregation and accumulation of IP 3 and phosphatidic acid. 8 All these cellular responses can be reproduced by the purified B-subunit moiety alone, suggesting that the non-catalytic binding domain of PTX is important in mediating these early cellular events.…”

Reversal of the CD4+/CD8+T-Cell Ratio in Lymph Node Cells upon In Vitro Mitogenic Stimulation by Highly Purified, Water-Soluble S3-S4 Dimer of Pertussis Toxin

“…induces T-cell proliferation to the same extent as PT (22,29,31,32,36). However, although the mitogenic effect of the B oligomer is well known, the roles of its individual components in the mitogenic function have not been extensively studied.…”

“…In contrast, PT-associated T-cell mitogenicity is mediated by the B oligomer (9, 31, 36) and appears to be independent of the enzymatic activity of the toxin, as inactivation of the S1 subunit by mutation has no effect on the mitogenic activity of PT (13,36), while alterations in the B oligomer can totally abrogate the mitogenic activity of PT (15,16,[20][21][22]. In addition, the B oligomer devoid of S1 induces T-cell proliferation to the same extent as PT (22,29,31,32,36). However, although the mitogenic effect of the B oligomer is well known, the roles of its individual components in the mitogenic function have not been extensively studied.…”