Evidence for An Interleukin-Independent Pathway for Human Lymphocyte Activation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 80; no. 11; pp. 3444 - 3447
• Main Authors: Koretzky, Gary A., Daniele, Ronald P., Greene, Warner C., Nowell, Peter C.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.06.1983; National Acad Sciences
• Subjects: Anti-Bacterial Agents - pharmacology; Antibodies; Calcimycin - pharmacology; Calcium; Cells, Cultured; Cultured cells; DNA Replication - drug effects; Fluorescent Antibody Technique; Humans; Interleukin-1 - physiology; Interleukin-2 - physiology; Lectins; Lymphocyte Activation - drug effects; Lymphocytes; Mitogens; Monoclonal antibodies; Monocytes; Receptors; T lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.80.11.3444

Though lectin mitogen stimulation of T-cell proliferation is an interleukin 1- (IL 1), interleukin 2- (IL 2) dependent process, the calcium ionophore A23187 may be able to initiate T-lymphocyte proliferation by an additional pathway. That the action of A23187 is IL 1 independent was demonstrated by its ability to stimulate monocyte-depleted cells without the addition of exogenous IL 1. The IL 2 independence of A23187 was indicated by (i) the inability of exogenous IL 2 to augment A23187-induced proliferation and (ii) the inability of the monoclonal antibody anti-Tac (with specificity for the human IL 2 receptor) to inhibit proliferation mediated by A23187. By contrast, in cultures stimulated with the lectin mitogen phytohemagglutinin, additional IL 2 considerably increased proliferation, whereas anti-Tac routinely caused 60-90% inhibition. Although the ionophore caused some IL 2 production and resulted in IL 2 receptor expression, quantitative studies showed that our results could not be explained by excessive amounts of endogenous IL 2 interfering with the blocking action of the antibody. Therefore, these data suggest that the action of A23187 as a human lymphocyte mitogen may be the result of at least two pathways--one dependent on the interleukin-cell interactions and the other independent of these mediators.