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. 1971 Oct 31;134(5):1266–1284. doi: 10.1084/jem.134.5.1266

CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE

VII. REQUIREMENT FOR DIFFERENTIATION OF THYMUS-DERIVED CELLS

J F A P Miller 1, J Sprent 1, A Basten 1, N L Warner 1, J C S Breitner 1, G Rowland 1, J Hamilton 1, H Silver 1, W J Martin 1
PMCID: PMC2139017  PMID: 5165203

Abstract

Experiments were designed to test the possibility that thymus-derived (T) cells cooperate with nonthymus derived (B) cells in antibody responses by acting as passive carriers of antigen. Thoracic duct lymphocytes (TDL) from fowl γG-tolerant mice were incubated in vitro with fowl anti-mouse lymphocyte globulin (FALG), which was shown not to be immunosuppressive in mice. On transfer into adult thymectomized, irradiated, and marrow protected (TxBM) hosts together with a control antigen, horse RBC, a response to horse RBC but not to fowl γG was obtained. By contrast, TxBM recipients of nontolerant, FALG-coated TDL responded to both antigens and the antibody-forming cells were shown to be derived from the host, not from the injected TDL. These findings suggested that, under the conditions of the experiment, triggering of unprimed B cells in the spleens of TxBM hosts was not achieved with antigen-coated tolerant lymphocytes. Another model utilized the ability of B cells to bind antibody-antigen complexes. Spleen cells from TxBM mice, incubated in vitro with anti-fowl γG-fowl γG·NIP, were injected with or without normal TDL (a source of T cells) into irradiated hosts. Only mice given both cell types could produce an anti-NIP antibody response. In a further experiment, spleen cells from HGG·NIP-primed mice were injected together with NIP-coated B cells (prepared as above) into irradiated hosts. A substantial anti-NIP antibody response occurred. If, however, the T cells in the spleens of HGG·NIP-primed mice were eliminated by treatment with anti-θ serum and complement, the NIP response was abolished. It was concluded that antigen-coated B cells could not substitute for T cells either in the primary or secondary response. Treatment of T cells from unprimed or primed mice with mitomycin C impaired their capacity to collaborate with B cells on transfer into irradiated hosts. Taken together these findings suggest that before collaboration can take place T cells must be activated by antigen to differentiate and in so doing may produce some factor essential for triggering of B cells.

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Selected References

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  1. BOYSE E. A., OLD L. J., CHOUROULINKOV I. CYTOTOXIC TEST FOR DEMONSTRATION OF MOUSE ANTIBODY. Methods Med Res. 1964;10:39–47. [PubMed] [Google Scholar]
  2. Basten A., Miller J. F., Warner N. L., Pye J. Specific inactivation of thymus-derived (T) and non-thymus-derived (B) lymphocytes by 125I-labelled antigen. Nat New Biol. 1971 May 26;231(21):104–106. doi: 10.1038/newbio231104a0. [DOI] [PubMed] [Google Scholar]
  3. Brownstone A., Mitchison N. A., Pitt-Rivers R. Chemical and serological studies with an iodine-containing synthetic immunological determinant 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) and related compounds. Immunology. 1966 May;10(5):465–479. [PMC free article] [PubMed] [Google Scholar]
  4. Byrt P., Ada G. L. An in vitro reaction between labelled flagellin or haemocyanin and lymphocyte-like cells from normal animals. Immunology. 1969 Oct;17(4):503–516. [PMC free article] [PubMed] [Google Scholar]
  5. Cheers C., Breitner J. C., Little M., Miller J. F. Cooperation between carrier-reactive and hapten-sensitive cells in vitro. Nat New Biol. 1971 Aug 25;232(34):248–250. doi: 10.1038/newbio232248a0. [DOI] [PubMed] [Google Scholar]
  6. Cunningham A. J., Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed] [Google Scholar]
  7. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dietrich F. M. The immune response to heterologous red cells in mice. Immunology. 1966 Apr;10(4):365–376. [PMC free article] [PubMed] [Google Scholar]
  9. Dresser D. W., Wortis D. H. Use of an antiglobulin serum to detect cells producing antibody with low haemolytic efficiency. Nature. 1965 Nov 27;208(5013):859–861. doi: 10.1038/208859a0. [DOI] [PubMed] [Google Scholar]
  10. Feldmann M., Easten A. The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response. J Exp Med. 1971 Jul 1;134(1):103–119. doi: 10.1084/jem.134.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. KERN M., EISEN H. N. The effect of antigenic stimulation on incorporation of phosphate and methionine into proteins of isolated lymph node cells. J Exp Med. 1959 Aug 1;110(2):207–219. doi: 10.1084/jem.110.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Katz D. H., Paul W. E., Goidl E. A., Benacerraf B. Radioresistance of cooperative function of carrier-specific lymphocytes in antihapten antibody responses. Science. 1970 Oct 23;170(3956):462–464. doi: 10.1126/science.170.3956.462. [DOI] [PubMed] [Google Scholar]
  13. MILLER J. F. Studies on mouse leukaemia. The role of the thymus in leukaemogenesis by cell-free leukaemic filtrates. Br J Cancer. 1960 Mar;14:93–98. doi: 10.1038/bjc.1960.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Martin W. J. Assay for the immunosuppressive capacity of antilymphocyte serum. I. Evidence for opsonization. J Immunol. 1969 Nov;103(5):979–989. [PubMed] [Google Scholar]
  15. Martin W. J., Miller J. F. Assay for the immunosuppressive capacity of antilymphocyte serum based on its action on thymus-derived cells. Int Arch Allergy Appl Immunol. 1969;35(2):163–178. doi: 10.1159/000230169. [DOI] [PubMed] [Google Scholar]
  16. Martin W. J., Miller J. F. Cell to cell interaction in the immune response. IV. Site of action of antilymphocyte globulin. J Exp Med. 1968 Oct 1;128(4):855–874. doi: 10.1084/jem.128.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miller J. F., Mitchell G. F. Cell to cell interaction in the immune response. I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J Exp Med. 1968 Oct 1;128(4):801–820. doi: 10.1084/jem.128.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller J. F., Mitchell G. F. Cell to cell interaction in the immune response. V. Target cells for tolerance induction. J Exp Med. 1970 Apr 1;131(4):675–699. doi: 10.1084/jem.131.4.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller J. F., Sprent J. Cell-to-cell interaction in the immune response. VI. Contribution of thymus-derived cells and antibody-forming cell precursors to immunological memory. J Exp Med. 1971 Jul 1;134(1):66–82. doi: 10.1084/jem.134.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller J. F., Sprent J. Thymus-derived cells in mouse thoracic duct lymph. Nat New Biol. 1971 Apr 28;230(17):267–270. doi: 10.1038/newbio230267a0. [DOI] [PubMed] [Google Scholar]
  21. Miller J. F., Warner N. L. The immune response of normal, irradiated and thymectomized mice to fowl immunoglobulin G as detected by a hemolytic plaque technique. Int Arch Allergy Appl Immunol. 1971;40(1):59–71. doi: 10.1159/000230395. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis. Eur J Immunol. 1971 Jan;1(1):10–17. doi: 10.1002/eji.1830010103. [DOI] [PubMed] [Google Scholar]
  24. Pasanen V. J., Mäkelä O. Effect of the number of haptens coupled to each erythrocyte on haemolytic plaque formation. Immunology. 1969 Mar;16(3):399–407. [PMC free article] [PubMed] [Google Scholar]
  25. REIF A. E., ALLEN J. M. THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES. J Exp Med. 1964 Sep 1;120:413–433. doi: 10.1084/jem.120.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sterzl J., Ríha I. Detection of cells producing 7S antibodies by the plaque technique. Nature. 1965 Nov 27;208(5013):858–859. doi: 10.1038/208858a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Valentine F. T., Lawrence H. S. Lymphocyte stimulation: transfer of cellular hypersensitivity to antigen in vitro. Science. 1969 Sep 5;165(3897):1014–1016. doi: 10.1126/science.165.3897.1014. [DOI] [PubMed] [Google Scholar]

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