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. 1979 Sep;64(3):812–819. doi: 10.1172/JCI109528

Prostaglandin E inhibition of T-lymphocyte colony formation: a possible mechanism of monocyte modulation of clonal expansion.

R S Bockman, M Rothschild
PMCID: PMC372186  PMID: 313939

Abstract

Prostaglandin and monocyte modulation of a T-lymphocyte cell capable of undergoing clonal expansion was studied. Circulating human mononuclear cells were isolated by density centrifugation. After 24 h in culture with phytohemagglutinin present, the cells were mixed with 0.3% agar and overlayed onto a 0.5% agar layer that contained media and phytohemagglutinin. At day 6, colonies that contained greater than 50 cells were counted. These colonies represented clonal prolifertion of a phytohemagglutinin-responsive T-lymphocyte precursor. This responder cell accounted for less than 0.3% of the starting cell population. Colonies were comprised of cells which, when isolated, formed E rosettes. These colony cells could be shown to have helper or suppressor function as measured by their ability to promote or inhibit immunoglobulin synthesis. By these latter criteria the colony cells were considered to be mature T lymphocytes. The addition of prostaglandin E to the cultures demonstrated a linear, r = 0.82, dose-dependent inhibition of colony formation with a 50% point of inhibition (I50) = 0.18 muM. Low numbers of normal monocytes when added to the cultures mimicked the effect of synthetic prostaglandin E2. A highly significant correlation could be shown for endogenous prostaglandin E levels and colony counts. It appears that monocytes through their synthesis of prostaglandin E2 can restrict the clonal expansion of a circulating T-lymphocyte precursor.

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Selected References

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  1. Bach F. H., Alter B. J., Solliday S., Zoschke D. C., Janis M. Lymphocyte reactivity in vitro. II. Soluble reconstituting factor permitting response of purified lymphocyte. Cell Immunol. 1970 Jul;1(2):219–227. doi: 10.1016/0008-8749(70)90009-2. [DOI] [PubMed] [Google Scholar]
  2. Beller D. I., Farr A. G., Unanue E. R. Regulation of lymphocyte proliferation and differentiation by macrophages. Fed Proc. 1978 Jan;37(1):91–96. [PubMed] [Google Scholar]
  3. Blyden G., Handschumacher R. E. Purification and properties of human lymphocyte activating factor (LAF). J Immunol. 1977 May;118(5):1631–1638. [PubMed] [Google Scholar]
  4. Bray M. A., Gordon D., Morley J. Proceedings: Role of prostaglandins in reactions of cellular immunity. Br J Pharmacol. 1974 Nov;52(3):453P–453P. [PMC free article] [PubMed] [Google Scholar]
  5. Calderon J., Kiely J. M., Lefko J. L., Unanue E. R. The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis. J Exp Med. 1975 Jul 1;142(1):151–164. doi: 10.1084/jem.142.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Claësson M. H., Rodger M. B., Johnson G. R., Whittingham S., Metcalf D. Colony formation by human T lymphocytes in agar medium. Clin Exp Immunol. 1977 Jun;28(3):526–534. [PMC free article] [PubMed] [Google Scholar]
  7. Farzad A., Penneys N. S., Ghaffar A., Ziboh V. A., Schlossberg J. PGE2 and PGF2alpha biosynthesis in stimulated and nonstimulated peritoneal preparations containing macrophages. Prostaglandins. 1977 Nov;14(5):829–837. doi: 10.1016/0090-6980(77)90300-8. [DOI] [PubMed] [Google Scholar]
  8. Fibach E., Gerassi E., Sachs L. Induction of colony formation in vitro by human lymphocytes. Nature. 1976 Jan 15;259(5539):127–129. doi: 10.1038/259127a0. [DOI] [PubMed] [Google Scholar]
  9. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goodwin J. S., Bankhurst A. D., Messner R. P. Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell. J Exp Med. 1977 Dec 1;146(6):1719–1734. doi: 10.1084/jem.146.6.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Humes J. L., Bonney R. J., Pelus L., Dahlgren M. E., Sadowski S. J., Kuehl F. A., Jr, Davies P. Macrophages synthesis and release prostaglandins in response to inflammatory stimuli. Nature. 1977 Sep 8;269(5624):149–151. doi: 10.1038/269149a0. [DOI] [PubMed] [Google Scholar]
  12. Kurland J. I., Bockman R. S., Broxmeyer H. E., Moore M. A. Limitation of excessive myelopoiesis by the intrinsic modulation of macrophage-derived prostaglandin E. Science. 1978 Feb 3;199(4328):552–555. doi: 10.1126/science.304600. [DOI] [PubMed] [Google Scholar]
  13. Kurland J. I., Bockman R. Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med. 1978 Mar 1;147(3):952–957. doi: 10.1084/jem.147.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurland J. I., Broxmeyer H. E., Pelus L. M., Bockman R. S., Moore M. A. Role for monocyte-macrophage-derived colony-stimulating factor and prostaglandin E in the positive and negative feedback control of myeloid stem cell proliferation. Blood. 1978 Aug;52(2):388–407. [PubMed] [Google Scholar]
  15. Kurland J. I., Kincade P. W., Moore M. A. Regulation of B-lymphocyte clonal proliferation by stimulatory and inhibitory macrophage-derived factors. J Exp Med. 1977 Nov 1;146(5):1420–1435. doi: 10.1084/jem.146.5.1420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurland J. I., Pelus L. M., Ralph P., Bockman R. S., Moore M. A. Induction of prostaglandin E synthesis in normal and neoplastic macrophages: role for colony-stimulating factor(s) distinct from effects on myeloid progenitor cell proliferation. Proc Natl Acad Sci U S A. 1979 May;76(5):2326–2330. doi: 10.1073/pnas.76.5.2326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kurland J., Moore M. A. Modulation of hemopoiesis by prostaglandins. Exp Hematol. 1977 Sep;5(5):357–373. [PubMed] [Google Scholar]
  18. Oppenheim J. J., Leventhal B. G., Hersh E. M. The transformation of column-purified lymphocytes with nonspecific and specific antigenic stimuli. J Immunol. 1968 Aug;101(2):262–267. [PubMed] [Google Scholar]
  19. Rozenszajn L. A., Shoham D., Kalechman I. Clonal proliferation of PHA-stimulated human lymphocytes in soft agar culture. Immunology. 1975 Dec;29(6):1041–1055. [PMC free article] [PubMed] [Google Scholar]
  20. Shen J., Wilson F., Shifrine M., Gershwin M. E. Select growth of human T lymphocytes in single phase semisolid culture. J Immunol. 1977 Oct;119(4):1299–1305. [PubMed] [Google Scholar]
  21. Siegal F. P., Siegal M. Enhancement by irradiated T cells of human plasma cell production: dissection of helper and suppressor functions in vitro. J Immunol. 1977 Feb;118(2):642–647. [PubMed] [Google Scholar]
  22. Sredni B., Kalechman Y., Michlin H., Rozenszajn L. A. Development of colonies in vitro of mitogen-stimulated mouse T lymphocytes. Nature. 1976 Jan 15;259(5539):130–132. doi: 10.1038/259130a0. [DOI] [PubMed] [Google Scholar]
  23. Sutherland D. C., Dalton G., Wilson J. D. T-lymphocyte colonies in malignant disease. Lancet. 1976 Nov 20;2(7995):1113–1115. doi: 10.1016/s0140-6736(76)91089-8. [DOI] [PubMed] [Google Scholar]
  24. Wilson J. D., Dalton G. Human T lymphocyte colonies in agar: a comparison with other T cell assays in healthy subjects and cancer patients. Aust J Exp Biol Med Sci. 1976 Feb;54(1):27–34. doi: 10.1038/icb.1976.3. [DOI] [PubMed] [Google Scholar]
  25. Wood D. D., Gaul S. L. Enhancement of the humoral response of T cell-depleted murine spleens by a factor derived from human monocytes in vitro. J Immunol. 1974 Sep;113(3):925–933. [PubMed] [Google Scholar]
  26. Zeevi A., Goldman I., Rozenszajn L. A. Stimulation and inhibition of human T-lymphocyte colony cell proliferation by hemopoietic cell factors. Cell Immunol. 1977 Feb;28(2):235–247. doi: 10.1016/0008-8749(77)90108-3. [DOI] [PubMed] [Google Scholar]

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