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. 1975 Jul 1;142(1):151–164. doi: 10.1084/jem.142.1.151

The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis

PMCID: PMC2189883  PMID: 1097572

Abstract

Culture fluids of peritoneal exudate cells rich in macrophages stimulated DNA synthesis of thymocytes and, to lesser extent, of spleen cells. We also investigated the effects of culture fluids from macrophages on the in vitro response to a hapten-carrier protein (fluorescein-menocyanin) using spleen cells from immune mice. Macrophage culture fluids contained an activity that increased the plaque-forming cell response of both IgG and IgM class. This increase was observed in the absence of any added hapten protein to the culture. The helper function of T lymphocytes (as evidenced by challenging with the hapten on the homologous carrier) was also increased by the macrophage culture fluid. However, this enhancement was best observed in conditions of relatively low T-cell activity. Also, the macrophage fluid allowed spleen cells of nude athymic mice to make a plaque- forming cell response to sheep red blood cells of both the IgM and IgG class. The macrophage was the cell source of the stimulatory molecule since it was generated only in cultures of macrophages devoid of significant number of lymphocytes. Stimulatory activity was not found in cultures of lymphocytes, mouse embryo cells, or 3T3 cells. The thymocyte stimulatory molecule did not contain H-2 antigens, was resistant to diisopropylfluorophosphate treatment, eluted from Sephadex with a size ranging from 15,000 to 21,000 daltons, and was sensitive to chymotrypsin and pepsin.

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Selected References

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  1. Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes. J Exp Med. 1974 Jul 1;140(1):19–37. doi: 10.1084/jem.140.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Armerding D., Sachs D. H., Katz D. H. Activation of T and B lymphocytes in vitro. III. Presence of Ia determinants on allogeneic effect factor. J Exp Med. 1974 Dec 1;140(6):1717–1722. doi: 10.1084/jem.140.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Askonas B. A., Roelants G. E. Macrophages bearing hapten-carrier molecules as foci inducers for T and B lymphocyte interaction. Eur J Immunol. 1974 Jan;4(1):1–4. doi: 10.1002/eji.1830040102. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Calderon J., Unanue E. R. Two biological activities regulating cell proliferation found in cultures of peritoneal exudate cells. Nature. 1975 Jan 31;253(5490):359–361. doi: 10.1038/253359a0. [DOI] [PubMed] [Google Scholar]
  6. Calderon J., Williams R. T., Unanue E. R. An inhibitor of cell proliferation released by cultures of macrophages. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4273–4277. doi: 10.1073/pnas.71.11.4273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen C., Hirsch J. G. The effects of mercaptoethanol and of peritoneal macrophages on the antibody-forming capacity of nonadherent mouse spleen cells in vitro. J Exp Med. 1972 Sep 1;136(3):604–617. doi: 10.1084/jem.136.3.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Geha R. S., Schneeberger E., Rosen F. S., Merler E. Interaction of human thymus-derived and non-thymus-derived lymphocytes in vitro. Induction of proliferation and antibody synthesis in B lymphocytes by a soluble factor released from antigen-stimulated T lymphocytes. J Exp Med. 1973 Nov 1;138(5):1230–1247. doi: 10.1084/jem.138.5.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gery I., Handschumacher R. E. Potentiation of the T lymphocyte response to mitogens. III. Properties of the mediator(s) from adherent cells. Cell Immunol. 1974 Mar 30;11(1-3):162–169. doi: 10.1016/0008-8749(74)90016-1. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Gordon S., Unkeless J. C., Cohn Z. A. Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process. J Exp Med. 1974 Oct 1;140(4):995–1010. doi: 10.1084/jem.140.4.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoffmann M., Dutton R. W. Immune response restoration with macrophage culture supernatants. Science. 1971 Jun 4;172(3987):1047–1048. doi: 10.1126/science.172.3987.1047. [DOI] [PubMed] [Google Scholar]
  14. Hunter P., Kettman J. R. Mode of action of a supernatant activity from T-cell cultures that nonspecifically stimulates the humoral immune response. Proc Natl Acad Sci U S A. 1974 Feb;71(2):512–516. doi: 10.1073/pnas.71.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Katz D. H., Unanue E. R. Critical role of determinant presentation in the induction of specific responses in immunocompetent lymphocytes. J Exp Med. 1973 Apr 1;137(4):967–990. doi: 10.1084/jem.137.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. March S. C., Parikh I., Cuatrecasas P. A simplified method for cyanogen bromide activation of agarose for affinity chromatography. Anal Biochem. 1974 Jul;60(1):149–152. doi: 10.1016/0003-2697(74)90139-0. [DOI] [PubMed] [Google Scholar]
  17. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Munro A. J., Taussig M. J., Campbell R., Williams H., Lawson Y. Antigen-specific T-cell factor in cell cooperation: physical properties and mapping in the left-hand (K) half of H-2. J Exp Med. 1974 Dec 1;140(6):1579–1587. doi: 10.1084/jem.140.6.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rubin A. S., MacDonald A. B., Coons A. H. Specific heterologous enhancement of immune responses. V. Isolation of a soluble enhancing factor from supernatants of specifically stimulated and allogeneically induced lymphoid cells. J Immunol. 1973 Nov;111(5):1314–1325. [PubMed] [Google Scholar]
  21. Schrader J. W. Mechanism of activation of the bone marrow-derived lymphocyte. 3. A distinction between a macrophage-produced triggering signal and the amplifying effect on triggered B lymphocytes of allogeneic interactions. J Exp Med. 1973 Dec 1;138(6):1466–1480. doi: 10.1084/jem.138.6.1466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shevach E. M., Rosenthal A. S. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med. 1973 Nov 1;138(5):1213–1229. doi: 10.1084/jem.138.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Spitznagel J. K., Allison A. C. Mode of action of adjuvants: effects on antibody responses to macrophage-associated bovine serum albumin. J Immunol. 1970 Jan;104(1):128–139. [PubMed] [Google Scholar]
  24. Unanue E. R., Askonas B. A., Allison A. C. A role of macrophages in the stimulation of immune responses by adjuvants. J Immunol. 1969 Jul;103(1):71–78. [PubMed] [Google Scholar]
  25. Unanue E. R., Cerottini J. C. The immunogenicity of antigen bound to the plasma membrane of macrophages. J Exp Med. 1970 Apr 1;131(4):711–725. doi: 10.1084/jem.131.4.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Unanue E. R. The regulatory role of macrophages in antigenic stimulation. Adv Immunol. 1972;15:95–165. doi: 10.1016/s0065-2776(08)60684-7. [DOI] [PubMed] [Google Scholar]
  27. Waldmann H., Munro A. T cell-dependent mediator in the immune response. II. Physical and biological properties. Immunology. 1974 Jul;27(1):53–64. [PMC free article] [PubMed] [Google Scholar]
  28. Watson J. The role of humoral factors in the initiation of in vitro primary immune responses. 3. Characterization of factors that replace thymus-derived cells. J Immunol. 1973 Nov;111(5):1301–1313. [PubMed] [Google Scholar]
  29. 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]

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