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. 1973 Nov 30;138(6):1481–1495. doi: 10.1084/jem.138.6.1481

THE ABILITY OF BACTERIAL LIPOPOLYSACCHARIDE TO MODULATE THE INDUCTION OF UNRESPONSIVENESS TO A STATE OF IMMUNITY

CELLULAR PARAMETERS

J A Louis 1, J M Chiller 1, W O Weigle 1
PMCID: PMC2139451  PMID: 4128441

Abstract

Studies were performed to define the cellular parameters involved in the interference with the induction of immunologic unresponsiveness to human gamma globulin (HGG) by bacterial lipopolysaccharide (LPS). Mice which were injected with deaggregated HGG (tolerogen) and with LPS did not become tolerant to that antigen, but rather became primed to a subsequent challenge with immunogen. The ability to prime with tolerogen and LPS was also demonstrated in an adoptive transfer system. The temporal relationship between the injection of tolerogen and that of LPS was critical for priming to occur. The injection of tolerogen and LPS not only primed mice to HGG, but also resulted in a primary antibody response to HGG. The capacity of LPS to interfere with the induction of tolerance was restricted to B cells and did not affect the ability to induce unresponsiveness in T cells. The secondary response to HGG in mice primed by tolerogen and LPS was found to be T-cell independent. These observations are interpreted and discussed from the standpoint of the ability of LPS to circumvent required T-cell cooperation and to modulate to tolerogenic stimulus into an immunogenic signal.

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Selected References

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

  1. Allison A. C., Davies A. J. Requirement of thymus-dependent lymphocytes for potentiation by adjuvants of antibody formation. Nature. 1971 Oct 1;233(5318):330–332. doi: 10.1038/233330a0. [DOI] [PubMed] [Google Scholar]
  2. Andersson B., Blomgren H. Evidence for a small pool of immunocompetent cells in the mouse thymus. Its role in the humoral antibody response against sheep erythrocytes, bovine serum albumin, ovalbumin and the NIP determinant. Cell Immunol. 1970 Oct;1(4):362–371. doi: 10.1016/0008-8749(70)90014-6. [DOI] [PubMed] [Google Scholar]
  3. Andersson J., Möller G., Sjöberg O. Selective induction of DNA synthesis in T and B lymphocytes. Cell Immunol. 1972 Aug;4(4):381–393. doi: 10.1016/0008-8749(72)90040-8. [DOI] [PubMed] [Google Scholar]
  4. Bretscher P., Cohn M. A theory of self-nonself discrimination. Science. 1970 Sep 11;169(3950):1042–1049. doi: 10.1126/science.169.3950.1042. [DOI] [PubMed] [Google Scholar]
  5. Brooke M. S. Conversion of immunological paralysis to immunity by endotoxin. Nature. 1965 May 8;206(984):635–636. doi: 10.1038/206635a0. [DOI] [PubMed] [Google Scholar]
  6. CLAMAN H. N. TOLERANCE TO A PROTEIN ANTIGEN IN ADULT MICE AND THE EFFECT OF NONSPECIFIC FACTORS. J Immunol. 1963 Dec;91:833–839. [PubMed] [Google Scholar]
  7. Chan E. L., Mishell R. I., Mitchell G. F. Cell interaction in an immune response in vitro: requirement for theta-carrying cells. Science. 1970 Dec 11;170(3963):1215–1217. doi: 10.1126/science.170.3963.1215. [DOI] [PubMed] [Google Scholar]
  8. Chiller J. M., Habicht G. S., Weigle W. O. Cellular sites of immunologic unresponsiveness. Proc Natl Acad Sci U S A. 1970 Mar;65(3):551–556. doi: 10.1073/pnas.65.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chiller J. M., Habicht G. S., Weigle W. O. Kinetic differences in unresponsiveness of thymus and bone marrow cells. Science. 1971 Feb 26;171(3973):813–815. doi: 10.1126/science.171.3973.813. [DOI] [PubMed] [Google Scholar]
  10. Chiller J. M., Skidmore B. J., Morrison D. C., Weigle W. O. Relationship of the structure of bacterial lipopolysaccharides to its function in mitogenesis and adjuvanticity. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2129–2133. doi: 10.1073/pnas.70.7.2129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chiller J. M., Weigle W. O. Cellular events during induction of immunologic unresponsiveness in adult mice. J Immunol. 1971 Jun;106(6):1647–1653. [PubMed] [Google Scholar]
  12. Chiller J. M., Weigle W. O. Termination of tolerance to human gamma globulin in mice by antigen and bacterial lipopolysaccharide (endotoxin). J Exp Med. 1973 Mar 1;137(3):740–750. doi: 10.1084/jem.137.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cohen A., Schlesinger M. Absorption of guinea pig serum with agar. A method for elimination of itscytotoxicity for murine thymus cells. Transplantation. 1970 Jul;10(1):130–132. doi: 10.1097/00007890-197007000-00027. [DOI] [PubMed] [Google Scholar]
  14. Cohen J. J., Claman H. N. Thymus-marrow immunocompetence. V. Hydrocortisone-resistant cells and processes in the hemolytic antibody response of mice. J Exp Med. 1971 May 1;133(5):1026–1034. doi: 10.1084/jem.133.5.1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cooper M. D., Lawton A. R., Kincade P. W. A two-stage model for development of antibody-producing cells. Clin Exp Immunol. 1972 May;11(1):143–149. [PMC free article] [PubMed] [Google Scholar]
  16. DIETRICH F. M., WEIGLE W. O. IMMUNOLOGIC UNRESPONSIVENESS TO HETEROLOGOUS SERUM PROTEINS INDUCED IN ADULT MICE AND TRANSFER OF THE UNRESPONSIVE STATE. J Immunol. 1964 Feb;92:167–172. [PubMed] [Google Scholar]
  17. DRESSER D. W. Effectiveness of lipid and lipidophilic substances as adjuvants. Nature. 1961 Sep 16;191:1169–1171. doi: 10.1038/1911169a0. [DOI] [PubMed] [Google Scholar]
  18. Gery I., Krüger J., Spiesel S. Z. Stimulation of B-lymphocytes by endotoxin. Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T 6 T 6 thymus grafts. J Immunol. 1972 Apr;108(4):1088–1091. [PubMed] [Google Scholar]
  19. Golub E. S., Mishell R. I., Weigle W. O., Dutton R. W. A modification of the hemolytic plaque assay for use with protein antigens. J Immunol. 1968 Jan;100(1):133–137. [PubMed] [Google Scholar]
  20. Golub E. S., Weigle W. O. Studies on the induction of immunologic unresponsiveness. I. Effects of endotoxin and phytochemagglutinin. J Immunol. 1967 Jun;98(6):1241–1247. [PubMed] [Google Scholar]
  21. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  22. Jones J. M., Kind P. D. Enhancing effect of bacterial endotoxins on bone marrow cells in the immune response to SRBC. J Immunol. 1972 May;108(5):1453–1455. [PubMed] [Google Scholar]
  23. Katz D. H., Hamaoka T., Benacerraf B. Immunological tolerance in bone marrow-derived lymphocytes. I. Evidence for an intracellular mechanism of inactivation of hapten-specific precursors of antibody-forming cells. J Exp Med. 1972 Dec 1;136(6):1404–1429. doi: 10.1084/jem.136.6.1404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Louis J., Chiller J. M., Weigle W. O. Fate of antigen-binding cells in unresponsive and immune mice. J Exp Med. 1973 Feb 1;137(2):461–469. doi: 10.1084/jem.137.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. MCPHERSON C. W. REDUCTION OF PSEUDOMONAS AERUGINOSA AND COLIFORM BACTERIA IN MOUSE DRINKING WATER FOLLOWING TREATMENT WITH HYDROCHLORIC ACID OR CHLORINE. Lab Anim Care. 1963 Oct;13:737–744. [PubMed] [Google Scholar]
  26. Mitchell G. F., Grumet F. C., McDevitt H. O. Genetic control of the immune response. The effect of thymectomy on the primary and secondary antibody response of mice to poly-L(tyr, glu)-poly-D, L-ala--poly-L-lys. J Exp Med. 1972 Jan;135(1):126–135. doi: 10.1084/jem.135.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mitchell G. F., Miller J. F. Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J Exp Med. 1968 Oct 1;128(4):821–837. doi: 10.1084/jem.128.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Möller G., Andersson J., Sjöberg O. Lipopolysaccharides can convert heterologous red cells into thymus-independent antigens. Cell Immunol. 1972 Aug;4(4):416–424. doi: 10.1016/0008-8749(72)90043-3. [DOI] [PubMed] [Google Scholar]
  29. Osborne D. P., Jr, Katz D. H. The allogeneic effect in inbred mice. 3. Unique antigenic structural requirements in the expression of the phenomenon on unprimed cell populations in vivo. J Exp Med. 1973 Apr 1;137(4):991–1008. doi: 10.1084/jem.137.4.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Plotz P. H., Talal N., Asofsky R. Assignment of direct and facilitated hemolytic plaques in mice to specific immunoglobulin classes. J Immunol. 1968 Apr;100(4):744–751. [PubMed] [Google Scholar]
  31. Schmidtke J. R., Dixon F. J. Immune response to a hapten coupled to a nonimmunogenic carrier. Influence of lipopolysaccharide. J Exp Med. 1972 Aug 1;136(2):392–397. doi: 10.1084/jem.136.2.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schrader J. W. Specific activation of the bone marrow-derived lymphocyte by antigen presented in a non-multivalent form. J Exp Med. 1973 Mar 1;137(3):844–849. doi: 10.1084/jem.137.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sjöberg O., Andersson J., Möller G. Lipopolysaccharide can substitute for helper cells in the antibody response in vitro. Eur J Immunol. 1972 Aug;2(4):326–331. doi: 10.1002/eji.1830020406. [DOI] [PubMed] [Google Scholar]
  34. Takahashi T., Carswell E. A., Thorbecke G. J. Surface antigens of immunocompetent cells. I. Effect of theta and PC.1 alloantisera on the ability of spleen cells to transfer immune responses. J Exp Med. 1970 Dec 1;132(6):1181–1190. doi: 10.1084/jem.132.6.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Van Boxel J. A., Stobo J. D., Paul W. E., Green I. Antibody-dependent lymphoid cell-mediated cytotoxicity: no requirement for thymus-derived lymphocytes. Science. 1972 Jan 14;175(4018):194–196. doi: 10.1126/science.175.4018.194. [DOI] [PubMed] [Google Scholar]
  36. Watson J., Trenkner E., Cohn M. The use of bacterial lipopolysaccharides to show that two signals are required for the induction of antibody synthesis. J Exp Med. 1973 Sep 1;138(3):699–714. doi: 10.1084/jem.138.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]

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