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. 1975 Aug 1;142(2):261–274. doi: 10.1084/jem.142.2.261

Induction of T-lymphocyte responses to a small molecular weight antigen. II. specific tolerance induced in azebenzenearsonate (ABA)- specific T cells in Guniea pigs by administration of low doses of an ABA conjugate of chloroacetyl tyrosine in incomplete Freund's adjuvant

PMCID: PMC2189895  PMID: 806648

Abstract

The experiments presented in this paper demonstrate that the induction of tolerance on the one hand and the induction of delayed sensitivity on the other hand can be accomplished by administration of similar doses of azobenzene-arsonate conjugated to N-chloracetyl tyrosine (ABA- T) to guinea pigs with the determining factor being the absence or presence, respectively, of activating bacterial products in the adjuvant mixture used. Thus, complete, persistent ABA-T-specific T-cell tolerance can be induced in adult guinea pigs with 20 mug of ABA-T given intradermally in incomplete Freund's adjuvant (IFA) whereas this same dose of ABA-T induces ABA-specific immunity when administered in complete Freund's adjuvant. This tolerance was not reversible by administration of ABA-T and IFA in the presence of bacterial lipopolysaccharide, was generated before the formation of primed T cells, and persisted for at least 3 mo after initiation. Moreover, cell transfer studies performed herein demonstrate that the unresponsiveness resulting from administration of ABA-T in IFA reflects the activity of suppressor cells to induce and maintain a state of unresponsiveness could only be demonstrated in unprimed animals may indicate a severe limitation on the potential clinical usefulness of such an approach to regulation of the immune system.

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Selected References

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  1. Alkan S. S., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response: the capacity of L-tyrosine-azobenzenearsonate to serve as a carrier for a macromolecular hapten. J Immunol. 1971 Aug;107(2):353–358. [PubMed] [Google Scholar]
  2. Alkan S. S., Williams E. B., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response. Humoral and cellular immune responses to small mono- and bifunctional antigen molecules. J Exp Med. 1972 Jun 1;135(6):1228–1246. doi: 10.1084/jem.135.6.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. I. Regulatory influence of bacterial lipopolysaccharide (LPS) on specific T-cell helper function. J Exp Med. 1974 Jan 1;139(1):24–43. doi: 10.1084/jem.139.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BENACERRAF B., OJEDA A., MAURER P. H. STUDIES ON ARTIFICIAL ANTIGENS. II. THE ANTIGENICITY IN GUINEA PIGS OF ARSANILIC ACID CONJUGATES OF COPOLYMERS OF D- OR L-ALPHA-AMINO ACIDS. J Exp Med. 1963 Dec 1;118:945–952. doi: 10.1084/jem.118.6.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Basten A., Miller J. F., Sprent J., Cheers C. Cell-to-cell interaction in the immune response. X. T-cell-dependent suppression in tolerant mice. J Exp Med. 1974 Jul 1;140(1):199–217. doi: 10.1084/jem.140.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Benacerraf B., Katz D. H. Failure to induce tolerance to 2,4-dinitrochlorobenzene contact sensitivity with a 2,4-dinitrophenyl (DNP) conjugate of a copolymer of D-glutamic acid and D-lysine, a specific tolerogen for DNP B cells. J Immunol. 1974 Mar;112(3):1158–1163. [PubMed] [Google Scholar]
  8. Borek F., Stupp Y. Specificity of delayed reactions to hapten-polypeptide conjugates. Immunochemistry. 1965 Dec;2(4):323–328. doi: 10.1016/0019-2791(65)90032-7. [DOI] [PubMed] [Google Scholar]
  9. Bullock W. W., Katz D. H., Benacerraf B. Induction of T-lymphocyte responses to a small molecular weight antigen. III. T-T cell interactions to determinants linked together: suppression vs. enhancement. J Exp Med. 1975 Aug 1;142(2):275–287. doi: 10.1084/jem.142.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Collotti C., Leskowitz S. The role of immunogenicity in the induction of tolerance with conjugates of arsanilic acid. J Exp Med. 1970 Mar 1;131(3):571–582. doi: 10.1084/jem.131.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DRESSER D. W. Specific inhibition of antibody production. II. Paralysis induced in adult mice by small quantities of protein antigen. Immunology. 1962 May;5:378–388. [PMC free article] [PubMed] [Google Scholar]
  13. Hamaoka T., Katz D. H. Cellular site of action of various adjuvants in antibody responses to hapten-carrier conjugates. J Immunol. 1973 Nov;111(5):1554–1563. [PubMed] [Google Scholar]
  14. Hanna N., Leskowitz S. Cooperative effects in antibody formation produced by hapten-specific delayed sensitivity. J Immunol. 1973 Aug;111(2):410–415. [PubMed] [Google Scholar]
  15. Hanna N., Leskowitz S. Structural requirements for in vivo and in vitro immunogenicity in hapten-specific delayed hypersensitivity. Cell Immunol. 1973 May;7(2):189–197. doi: 10.1016/0008-8749(73)90241-4. [DOI] [PubMed] [Google Scholar]
  16. Jones V. E., Leskowitz S. Immunochemical study of antigenic specificity in delayed hypersensitivity. IV. The production of unresponsiveness to delayed hypersensitivity with a single antigenic determinant. J Exp Med. 1965 Sep 1;122(3):505–515. doi: 10.1084/jem.122.3.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Katz S. I., Parker D., Sommer G., Turk J. L. Suppressor cells in normal immunisation as a basic homeostatic phenomenon. Nature. 1974 Apr 12;248(449):612–614. doi: 10.1038/248612a0. [DOI] [PubMed] [Google Scholar]
  18. Loewi G., Holborow E. J., Temple A. Inhibition of delayed hypersensitivity by pre-immunization without complete adjuvant. Immunology. 1966 Apr;10(4):339–347. [PMC free article] [PubMed] [Google Scholar]
  19. Nauciel C., Fleck J., Martin J. P., Mock M., Nguyen-Huy H. Adjuvant activity of bacterial peptidoglycans on the production of delayed hypersensitivity and on antibody response. Eur J Immunol. 1974 May;4(5):352–356. doi: 10.1002/eji.1830040509. [DOI] [PubMed] [Google Scholar]
  20. Neta R., Salvin S. B. Specific depression of delayed hypersensitivity to purified proteins, with relation to production of circulating antibody. Cell Immunol. 1973 Nov;9(2):242–250. doi: 10.1016/0008-8749(73)90075-0. [DOI] [PubMed] [Google Scholar]
  21. Newburger P. E., Hamaoka T., Katz D. H. Potentiation of helper T cell function in IgE antibody responses by bacterial lipolysaccharide (LPS). J Immunol. 1974 Sep;113(3):824–829. [PubMed] [Google Scholar]
  22. Phanuphak P., Moorhead J. W., Claman H. N. Tolerance and contact sensitivity to DNFB in mice. I. In vivo detection by ear swelling and correlation with in vitro cell stimulation. J Immunol. 1974 Jan;112(1):115–123. [PubMed] [Google Scholar]
  23. TABACHNICK M., SOBOTKA H. Azoproteins. I. Spectrophotometric studies of amino acid azo derivatives. J Biol Chem. 1959 Jul;234(7):1726–1730. [PubMed] [Google Scholar]
  24. TABACHNICK M., SOBOTKA H. Azoproteins. II. A spectrophotometric study of the coupling of diazotized arsanilic acid with proteins. J Biol Chem. 1960 Apr;235:1051–1054. [PubMed] [Google Scholar]
  25. Zembala M., Asherson G. L. Depression of the T cell phenomenon of contact sensitivity by T cells from unresponsive mice. Nature. 1973 Jul 27;244(5413):227–228. doi: 10.1038/244227a0. [DOI] [PubMed] [Google Scholar]

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