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Inhibition of transformed T cell growth in vitro by monoclonal antibodies directed against distinct activating molecules
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 140(1)
- Publication Year :
- 1988
-
Abstract
- Stimulatory of antigen-specific murine T cell hybridomas with the appropriate antigen has been shown to cause lymphokine secretion and inhibition of spontaneous cell growth. In this study, the effect of cellular activation on the growth of transformed T cells, of known or unknown antigen specificity, was explored with stimulatory monoclonal antibodies (mAb) that recognize nonclonally distributed T cell surface molecules. Anti-CD3 antibodies stimulated interleukin 2 (IL-2) secretion while they inhibited murine and human T cell tumor growth in vitro. Both responses required external cross-linking of the anti-CD3 antibodies. Activation via two molecules that are not physically associated with the T cell antigen receptor, Thy-1 and Ly-6, also inhibited transformed T cell growth while inducing IL-2 secretion. Notably, an anti-Thy-1 mAb that did not cause the transformed T cells to secrete lymphokines failed to affect their growth, and in fact blocked the growth inhibition induced by the stimulatory mAb. Regardless of which stimulating mAb was used, IL-2 production and cell growth were inversely proportional, manifesting similar antibody dose-response curves. Activation of a T cell hybridoma with stimulatory mAb resulted in rapid lysis, as evidenced by the release of 51Cr and lactate dehydrogenase. Cell cycle analysis demonstrated that cellular activation was accompanied by a cell cycle block between the G1 and S phases, and probably a slowing of the transit of cells already in S. These results demonstrate that the growth of a spectrum of neoplastic T cells, murine and human, can be inhibited by what are normally growth-promoting signals for non-transformed T cells.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Hybridomas
CD3 Complex
Cell Survival
T-Lymphocytes
Cell Cycle
Antibodies, Monoclonal
DNA
Receptors, Fc
Lymphocyte Activation
Antigens, Differentiation
Antigen-Antibody Reactions
Mice
Cell Transformation, Neoplastic
Antigens, Surface
Animals
Antigens, Ly
Interleukin-2
Thy-1 Antigens
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 140
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.pmid..........d37700adc7381059eb7cfd81f0ed05f3