Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Dec;90(3):497–502. doi: 10.1111/j.1365-2249.1992.tb05873.x

Haemorrhage-induced alterations in function and cytokine production of T cells and T cell subpopulations.

E Abraham 1, Y H Chang 1
PMCID: PMC1554572  PMID: 1360880

Abstract

Haemorrhage produces alterations in macrophage, T and B cell function. In order to better define the mechanism for the effects of blood loss on immune response, we examined function of and cytokine production by purified T cells, CD4+ and CD8+ subpopulations after blood loss. Whereas T and CD4+ cells from control, unhaemorrhaged animals produced no alteration in proliferation when added to cultures of mitogen-stimulated splenocytes from normal mice, proliferation was decreased when T or CD4+ cells from haemorrhaged mice were included. The addition of CD8+ cells from haemorrhaged animals to mitogen-stimulated cultures reduced proliferation by approximately 50% more than that found when CD8+ cells from control, unhaemorrhaged animals were included. Supernatants of mitogen-stimulated splenocytes from haemorrhaged mice contained significantly less IL-2 and interferon-gamma (IFN-gamma) than did those from control, unhaemorrhaged mice. CD4+ populations from haemorrhaged mice produced significantly more IL-10, and significantly less IFN-gamma, than did CD4+ cells from control, unhaemorrhaged mice. There were no significant differences in IL-2, IL-4, IL-10 or IFN-gamma production by CD8+ cells from haemorrhaged or control mice. The present experiments demonstrate that haemorrhage affects both CD4+ and CD8+ T cell subsets. In particular, haemorrhage appeared to activate CD4+, Th2 cells, with concomitant suppression of the Th1 subpopulation. These results provide a mechanism which may contribute to the alterations in cytokine production previously described to occur following blood loss.

Full text

PDF
497

Selected References

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

  1. Abraham E., Chang Y. H. Cellular and humoral bases of hemorrhage-induced depression of lymphocyte function. Crit Care Med. 1986 Feb;14(2):81–86. doi: 10.1097/00003246-198602000-00001. [DOI] [PubMed] [Google Scholar]
  2. Abraham E., Chang Y. H. Generation of functionally active suppressor cells by haemorrhage and haemorrhagic serum. Clin Exp Immunol. 1988 May;72(2):238–242. [PMC free article] [PubMed] [Google Scholar]
  3. Abraham E., Chang Y. H. Hemorrhage in mice produces alterations in intestinal B cell repertoires. Cell Immunol. 1990 Jun;128(1):165–174. doi: 10.1016/0008-8749(90)90015-j. [DOI] [PubMed] [Google Scholar]
  4. Abraham E., Chang Y. H. Modulation of the posthemorrhage bacterial polysaccharide antigen-specific antibody response by interleukins 2 and 4. Lymphokine Cytokine Res. 1992 Aug;11(4):241–246. [PubMed] [Google Scholar]
  5. Abraham E., Freitas A. A., Coutinho A. A. Hemorrhage in mice produces alterations in B cell repertoires. Cell Immunol. 1989 Aug;122(1):208–217. doi: 10.1016/0008-8749(89)90161-5. [DOI] [PubMed] [Google Scholar]
  6. Abraham E., Freitas A. A. Hemorrhage produces abnormalities in lymphocyte function and lymphokine generation. J Immunol. 1989 Feb 1;142(3):899–906. [PubMed] [Google Scholar]
  7. Abraham E., Freitas A. A., Jagels M., Chang Y. H. Transfer of T or CD8+ cells from hemorrhaged mice produce alterations in bacterial antigen specific plasma cell repertoires in normal syngeneic recipients. Immunobiology. 1990 Nov;181(4-5):379–387. doi: 10.1016/S0171-2985(11)80506-1. [DOI] [PubMed] [Google Scholar]
  8. Abraham E. Host defense abnormalities after hemorrhage, trauma, and burns. Crit Care Med. 1989 Sep;17(9):934–939. doi: 10.1097/00003246-198909000-00020. [DOI] [PubMed] [Google Scholar]
  9. Abraham E., Lee R. J., Chang Y. H. The role of interleukin 2 in hemorrhage-induced abnormalities of lymphocyte proliferation. Circ Shock. 1986;18(3):205–213. [PubMed] [Google Scholar]
  10. Abraham E., Richmond N. J., Chang Y. H. Effects of hemorrhage on interleukin-1 production. Circ Shock. 1988 May;25(1):33–40. [PubMed] [Google Scholar]
  11. Abraham E., Robinson A. Oral immunization with bacterial polysaccharide and adjuvant enhances antigen-specific pulmonary secretory antibody response and resistance to pneumonia. Vaccine. 1991 Oct;9(10):757–764. doi: 10.1016/0264-410x(91)90293-f. [DOI] [PubMed] [Google Scholar]
  12. Ayala A., Perrin M. M., Chaudry I. H. Defective macrophage antigen presentation following haemorrhage is associated with the loss of MHC class II (Ia) antigens. Immunology. 1990 May;70(1):33–39. [PMC free article] [PubMed] [Google Scholar]
  13. Ayala A., Perrin M. M., Wagner M. A., Chaudry I. H. Enhanced susceptibility to sepsis after simple hemorrhage. Depression of Fc and C3b receptor-mediated phagocytosis. Arch Surg. 1990 Jan;125(1):70–75. doi: 10.1001/archsurg.1990.01410130076010. [DOI] [PubMed] [Google Scholar]
  14. Chang Y. H., Jagels M., Abraham E. Haemorrhage produces depressions in alloantigen-specific immune responses in the mouse through activation of suppressor T cells. Clin Exp Immunol. 1990 Jun;80(3):478–483. doi: 10.1111/j.1365-2249.1990.tb03313.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chaudry I. H., Ayala A., Ertel W., Stephan R. N. Hemorrhage and resuscitation: immunological aspects. Am J Physiol. 1990 Oct;259(4 Pt 2):R663–R678. doi: 10.1152/ajpregu.1990.259.4.R663. [DOI] [PubMed] [Google Scholar]
  16. Defrance T., Vanbervliet B., Brière F., Durand I., Rousset F., Banchereau J. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med. 1992 Mar 1;175(3):671–682. doi: 10.1084/jem.175.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ertel W., Morrison M. H., Ayala A., Dean R. E., Chaudry I. H. Interferon-gamma attenuates hemorrhage-induced suppression of macrophage and splenocyte functions and decreases susceptibility to sepsis. Surgery. 1992 Feb;111(2):177–187. [PubMed] [Google Scholar]
  18. Ertel W., Morrison M. H., Ayala A., Perrin M. M., Chaudry I. H. Blockade of prostaglandin production increases cachectin synthesis and prevents depression of macrophage functions after hemorrhagic shock. Ann Surg. 1991 Mar;213(3):265–271. doi: 10.1097/00000658-199103000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fiorentino D. F., Zlotnik A., Mosmann T. R., Howard M., O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991 Dec 1;147(11):3815–3822. [PubMed] [Google Scholar]
  20. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  21. Howard M., O'Garra A. Biological properties of interleukin 10. Immunol Today. 1992 Jun;13(6):198–200. doi: 10.1016/0167-5699(92)90153-X. [DOI] [PubMed] [Google Scholar]
  22. Hu-Li J., Ohara J., Watson C., Tsang W., Paul W. E. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J Immunol. 1989 Feb 1;142(3):800–807. [PubMed] [Google Scholar]
  23. MacNeil I. A., Suda T., Moore K. W., Mosmann T. R., Zlotnik A. IL-10, a novel growth cofactor for mature and immature T cells. J Immunol. 1990 Dec 15;145(12):4167–4173. [PubMed] [Google Scholar]
  24. Meldrum D. R., Ayala A., Perrin M. M., Ertel W., Chaudry I. H. Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage. J Surg Res. 1991 Aug;51(2):158–164. doi: 10.1016/0022-4804(91)90088-4. [DOI] [PubMed] [Google Scholar]
  25. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  26. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  27. Pierres A., Naquet P., Van Agthoven A., Bekkhoucha F., Denizot F., Mishal Z., Schmitt-Verhulst A. M., Pierres M. A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones. J Immunol. 1984 Jun;132(6):2775–2782. [PubMed] [Google Scholar]
  28. Robinson A., Abraham E. Effects of haemorrhage on bacterial antigen specific pulmonary plasma cell function. Clin Exp Immunol. 1992 Apr;88(1):124–128. doi: 10.1111/j.1365-2249.1992.tb03050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Robinson A., Abraham E. Effects of hemorrhage and resuscitation on bacterial antigen-specific pulmonary plasma cell function. Crit Care Med. 1991 Oct;19(10):1285–1293. doi: 10.1097/00003246-199110000-00011. [DOI] [PubMed] [Google Scholar]
  30. Robinson A., Abraham E. Hemorrhage in mice produces alterations in pulmonary B cell repertoires. J Immunol. 1990 Dec 1;145(11):3734–3739. [PubMed] [Google Scholar]
  31. Romagnani S. Human TH1 and TH2 subsets: doubt no more. Immunol Today. 1991 Aug;12(8):256–257. doi: 10.1016/0167-5699(91)90120-I. [DOI] [PubMed] [Google Scholar]
  32. Stephan R. N., Kupper T. S., Geha A. S., Baue A. E., Chaudry I. H. Hemorrhage without tissue trauma produces immunosuppression and enhances susceptibility to sepsis. Arch Surg. 1987 Jan;122(1):62–68. doi: 10.1001/archsurg.1987.01400130068010. [DOI] [PubMed] [Google Scholar]
  33. Vieira P., de Waal-Malefyt R., Dang M. N., Johnson K. E., Kastelein R., Fiorentino D. F., deVries J. E., Roncarolo M. G., Mosmann T. R., Moore K. W. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172–1176. doi: 10.1073/pnas.88.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES