Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1975 Apr 1;141(4):821–839.

Effects on C-reactive protein on the lymphoid system. I. Binding to thymus-dependent lymphocytes and alteration of their functions

PMCID: PMC2189740  PMID: 1092791

Abstract

C-reactive protein (CRP) is an acute phase protein which shares with the immunoglobulins the ability to induce precipitation and agglutination reactions and activate the complement system. We report here that purified human CRP binds selectively to human T lymphocytes, inhibits their ability to form spontaneous rosettes with sheep erythrocytes and inhibits their response to allogeneic cells in mixed lymphocyte culture reactions; it fails to inhibit phytohemagglutinin- or concanavalin-A-induced mitogenesis. CRP does not bind to human B lymphocytes, nor does it alter the following B-cell functions: binding to activated complement components or the Fc portion of immunoglobulins, mediation of antibody-dependent cytotoxicity reactions or the ability of allogeneic cells to stimulate a mixed lymphocyte culture reaction. Human CRP shows similar selective binding with murine T lymphocytes. It therefore seems that binding of CRP is a property of T lymphocytes or a subpopulation thereof, and can result in modulation of certain of the T-cell functional characteristics in vitro. We suggest that CRP may play a role in modulating T-cell functions during the inflammatory state.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANDERSON H. C., McCARTY M. Determination of C-reactive protein in the blood as a measure of the activity of the disease process in acute rheumatic fever. Am J Med. 1950 Apr;8(4):445–455. doi: 10.1016/0002-9343(50)90226-9. [DOI] [PubMed] [Google Scholar]
  2. ANDERSON H. C., McCARTY M. The occurrence in the rabbit of an acute phase protein analogous to human C reactive protein. J Exp Med. 1951 Jan;93(1):25–36. doi: 10.1084/jem.93.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Abernethy T. J., Avery O. T. THE OCCURRENCE DURING ACUTE INFECTIONS OF A PROTEIN NOT NORMALLY PRESENT IN THE BLOOD : I. DISTRIBUTION OF THE REACTIVE PROTEIN IN PATIENTS' SERA AND THE EFFECT OF CALCIUM ON THE FLOCCULATION REACTION WITH C POLYSACCHARIDE OF PNEUMOCOCCUS. J Exp Med. 1941 Jan 31;73(2):173–182. doi: 10.1084/jem.73.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bach F. H., Segall M., Zier K. S., Sondel P. M., Alter B. J., Bach M. L. Cell mediated immunity: separation of cells involved in recognitive and destructive phases. Science. 1973 Apr 27;180(4084):403–406. doi: 10.1126/science.180.4084.403. [DOI] [PubMed] [Google Scholar]
  5. Bianco C., Patrick R., Nussenzweig V. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med. 1970 Oct 1;132(4):702–720. doi: 10.1084/jem.132.4.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boylston A. W. Theta antigen and immunogolbulin on a tissue-cultured mouse lymphoma. Immunology. 1973 May;24(5):851–857. [PMC free article] [PubMed] [Google Scholar]
  7. Brown G., Greaves M. F. Cell surface markers for human T and B lymphocytes. Eur J Immunol. 1974 Apr;4(4):302–310. doi: 10.1002/eji.1830040414. [DOI] [PubMed] [Google Scholar]
  8. Buckley R. H., Schiff R. I., Amos D. B. Blocking of autologous and homologous leukocyte responses by human alloimmune plasmas: a possible in vitro correlate of enhancement. J Immunol. 1972 Jan;108(1):34–44. [PubMed] [Google Scholar]
  9. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. II. Antigen triggering of T and B cells in vitro. J Immunol. 1974 Oct;113(4):1122–1127. [PubMed] [Google Scholar]
  10. Chisari F. V., Edgington T. S. Human T lymphocyte "E" rosette function. I. A process modulated by intracellular cyclic AMP. J Exp Med. 1974 Oct 1;140(4):1122–1126. doi: 10.1084/jem.140.4.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dickler H. B. Studies of the human lymphocyte receptor for heat-aggregated or antigen-complexed immunoglobulin. J Exp Med. 1974 Aug 1;140(2):508–522. doi: 10.1084/jem.140.2.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Falk L., Wright J., Wolfe L., Deinhardt F. Herpesvirus ateles: transformation in vitro of marmoset splenic lymphocytes. Int J Cancer. 1974 Aug 15;14(2):244–251. doi: 10.1002/ijc.2910140213. [DOI] [PubMed] [Google Scholar]
  14. Fletcher T. C., Baldo B. A. Immediate hypersensitivity responses in flatfish. Science. 1974 Jul 26;185(4148):360–361. doi: 10.1126/science.185.4148.360. [DOI] [PubMed] [Google Scholar]
  15. GAL K., MILTENYI M. Haemagglutination test for the demonstration of C-reactive protein. Acta Microbiol Acad Sci Hung. 1955;3(1-2):41–51. [PubMed] [Google Scholar]
  16. Gershon R. K., Cohen P., Hencin R., Liebhaber S. A. Suppressor T cells. J Immunol. 1972 Mar;108(3):586–590. [PubMed] [Google Scholar]
  17. Gotschlich E. C., Edelman G. M. Binding properties and specificity of C-reactive protein. Proc Natl Acad Sci U S A. 1967 Mar;57(3):706–712. doi: 10.1073/pnas.57.3.706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gotschlich E. C., Edelman G. M. C-reactive protein: a molecule composed of subunits. Proc Natl Acad Sci U S A. 1965 Aug;54(2):558–566. doi: 10.1073/pnas.54.2.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. HEDLUND P. Clinical and experimental studies on C-reactive protein (acute phase protein). Acta Med Scand Suppl. 1961;361:1–71. [PubMed] [Google Scholar]
  20. HOKAMA Y., COLEMAN M. K., RILEY R. F. In vitro effects of C-reactive protein on phagocytosis. J Bacteriol. 1962 May;83:1017–1024. doi: 10.1128/jb.83.5.1017-1024.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hartzman R. J., Segall M., Bach M. L., Bach F. H. Histocompatibility matching. VI. Miniaturization of the mixed leukocyte culture test: a preliminary report. Transplantation. 1971 Mar;11(3):268–273. doi: 10.1097/00007890-197103000-00005. [DOI] [PubMed] [Google Scholar]
  22. Heidelberger M., Gotschlich E. C., Higginbotham J. D. Inhibition experiments with pneumococcal C and depyruvylated type-IV polysaccharides. Carbohydr Res. 1972 Apr;22(1):1–4. doi: 10.1016/s0008-6215(00)85719-5. [DOI] [PubMed] [Google Scholar]
  23. Hokama Y., Paik Y. P., Kimura L., Yanagihara E. Effect of C-reactive protein and blood-group substances on 3 H-thymidine incorporation into DNA of leukocyte. J Reticuloendothel Soc. 1973 Feb;13(2):111–121. [PubMed] [Google Scholar]
  24. Hornung M. O. Growth inhibition of human melanoma cells by C-reactive protein (CRP) activated lymphocytes. Proc Soc Exp Biol Med. 1972 Apr;139(4):1166–1169. doi: 10.3181/00379727-139-36322. [DOI] [PubMed] [Google Scholar]
  25. Hornung M., Fritchi S. Isolation of C reactive protein and its effect on human lymphocytes in vitro. Nat New Biol. 1971 Mar 17;230(11):84–85. doi: 10.1038/newbio230084a0. [DOI] [PubMed] [Google Scholar]
  26. Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  28. Kaplan M. H., Volanakis J. E. Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol. 1974 Jun;112(6):2135–2147. [PubMed] [Google Scholar]
  29. Kehoe J. M., Fougereau M. Immunoglobulin peptide with complement fixing activity. Nature. 1969 Dec 20;224(5225):1212–1213. doi: 10.1038/2241212a0. [DOI] [PubMed] [Google Scholar]
  30. Kindmark C. O. Stimulating effect of C-reactive protein on phagocytosis of various species of pathogenic bacteria. Clin Exp Immunol. 1971 Jun;8(6):941–948. [PMC free article] [PubMed] [Google Scholar]
  31. Kushner I., Somerville J. A. Estimation of the molecular size of C-reactive protein and CX-reactive protein in serum. Biochim Biophys Acta. 1970 Apr 28;207(1):105–114. doi: 10.1016/0005-2795(70)90140-6. [DOI] [PubMed] [Google Scholar]
  32. Lohrmann H. P., Novikovs L., Graw R. G., Jr Stimulatory capacity of human T and B lymphocytes in the mixed leukocyte culture. Nature. 1974 Jul 12;250(462):144–146. doi: 10.1038/250144a0. [DOI] [PubMed] [Google Scholar]
  33. MacLennan I. C. Antibody in the induction and inhibition of lymphocyte cytotoxicity. Transplant Rev. 1972;13:67–90. doi: 10.1111/j.1600-065x.1972.tb00060.x. [DOI] [PubMed] [Google Scholar]
  34. Macleod C. M., Avery O. T. THE OCCURRENCE DURING ACUTE INFECTIONS OF A PROTEIN NOT NORMALLY PRESENT IN THE BLOOD : II. ISOLATION AND PROPERTIES OF THE REACTIVE PROTEIN. J Exp Med. 1941 Jan 31;73(2):183–190. doi: 10.1084/jem.73.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Macleod C. M., Avery O. T. THE OCCURRENCE DURING ACUTE INFECTIONS OF A PROTEIN NOT NORMALLY PRESENT IN THE BLOOD : III. IMMUNOLOGICAL PROPERTIES OF THE C-REACTIVE PROTEIN AND ITS DIFFERENTIATION FROM NORMAL BLOOD PROTEINS. J Exp Med. 1941 Jan 31;73(2):191–200. doi: 10.1084/jem.73.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McCarty M. THE OCCURRENCE DURING ACUTE INFECTIONS OF A PROTEIN NOT NORMALLY PRESENT IN THE BLOOD : IV. CRYSTALLIZATION OF THE C-REACTIVE PROTEIN. J Exp Med. 1947 Apr 30;85(5):491–498. doi: 10.1084/jem.85.5.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Patterson L. T., Harper J. M., Higginbotham R. D. Association of C-reactive protein and circulating leukocytes with resistance to Staphylococcus aureus infection in endotoxin-treated mice and rabbits. J Bacteriol. 1968 Apr;95(4):1375–1379. doi: 10.1128/jb.95.4.1375-1379.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Peavy D. L., Pierce C. W. Cell-mediated immune responses in vitro. I. Suppression of the generation of cytotoxic lymphocytes by concanavalin A and concanavalin A-activated spleen cells. J Exp Med. 1974 Aug 1;140(2):356–369. doi: 10.1084/jem.140.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Raff M. C., Wortis H. H. Thymus dependence of theta-bearing cells in the peripheral lymphoid tissues of mice. Immunology. 1970 Jun;18(6):931–942. [PMC free article] [PubMed] [Google Scholar]
  40. Raff M. Theta isoantigen as a marker of thymus-derived lymphocytes in mice. Nature. 1969 Oct 25;224(5217):378–379. doi: 10.1038/224378a0. [DOI] [PubMed] [Google Scholar]
  41. Revillard J. P., Robert M., Betuel H., Latour M., Bonneau M., Brochier J., Traeger J. Inhibition of the mixed lymphocyte reaction by antibodies. Transplant Proc. 1972 Jun;4(2):173–176. [PubMed] [Google Scholar]
  42. Ross G. D., Polley M. J., Rabellino E. M., Grey H. M. Two different complement receptors on human lymphocytes. One specific for C3b and one specific for C3b inactivator-cleaved C3b. J Exp Med. 1973 Oct 1;138(4):798–811. doi: 10.1084/jem.138.4.798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Siegel J., Rent R., Gewurz H. Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera. J Exp Med. 1974 Sep 1;140(3):631–647. doi: 10.1084/jem.140.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Thorsby E. The human major histocompatibility system. Transplant Rev. 1974;18:51–129. [PubMed] [Google Scholar]
  45. Tillett W. S., Francis T. SEROLOGICAL REACTIONS IN PNEUMONIA WITH A NON-PROTEIN SOMATIC FRACTION OF PNEUMOCOCCUS. J Exp Med. 1930 Sep 30;52(4):561–571. doi: 10.1084/jem.52.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Volanakis J. E., Kaplan M. H. Specificity of C-reactive protein for choline phosphate residues of pneumococcal C-polysaccharide. Proc Soc Exp Biol Med. 1971 Feb;136(2):612–614. doi: 10.3181/00379727-136-35323. [DOI] [PubMed] [Google Scholar]
  47. WOOD H. F. Effect of C-reactive protein on normal human leukocytes. Proc Soc Exp Biol Med. 1951 Apr;76(4):843–847. doi: 10.3181/00379727-76-18650. [DOI] [PubMed] [Google Scholar]
  48. WOOD H. F., McCARTY M., SLATER R. J. The occurrence during acute infections of a protein not normally present in the blood. V. Physical-chemical properties of the C-reactive protein crystallized by a modified technique. J Exp Med. 1954 Jul 1;100(1):71–79. doi: 10.1084/jem.100.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. WOOD H. F. The relationship between the acute phase response and antibody production in the rabbit. I. Correlation between the early appearance of Cx-reaction protein and subsequent antibody production. J Exp Med. 1953 Oct;98(4):311–319. doi: 10.1084/jem.98.4.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wernet P., Kunkel H. G. Antibodies to a specific surface antigen of T cells in human sera inhibiting mixed leukocyte culture reactions. J Exp Med. 1973 Oct 1;138(4):1021–1026. doi: 10.1084/jem.138.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zighelboim J., Bonavida B., Fahey J. L. Evidence for several cell populations active in antibody dependent cellular cytotoxicity. J Immunol. 1973 Dec;111(6):1737–1742. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES