THE SPECIFIC SELECTION OF RECIRCULATING LYMPHOCYTES BY ANTIGEN IN NORMAL AND PREIMMUNIZED RATS (original) (raw)

Abstract

Thoracic duct lymphocytes (TDL) from normal rats will restore a primary antibody response to sheep erythrocytes (SRBC) in irradiated recipients and cause a graft-_versus_-host reaction in F1 hybrid rats; lymphocytes from rats immunized with either tetanus toxoid or dinitrophenylated bovine gamma globulin (DNP BGG) will generate specific antibody after cell transfer and challenge. The ability of TDL to mediate each of these responses is severely depressed by giving a single intravenous dose of the specific antigen shortly before cannulation of the thoracic duct, although the lymphocyte donors themselves respond normally. The injection of antigen does not decrease the output of lymphocytes in the thoracic duct and the effect is specific for the antigen injected. The findings are most readily accounted for by assuming that small subpopulations of specific lymphocytes are selected from the recirculating pool by antigen which has localized in lymphoid tissue. The observation that passive antibody abolishes selection by SRBC supports this interpretation. The strong selection exerted by a subcutaneous injection of SRBC in Freund's complete adjuvant, which induces delayed hypersensitivity but little early antibody, suggests that a common cell type may be involved in the induction of both delayed hypersensitivity and antibody formation. The anti-DNP antibody response generated by TDL from rats immunized with DNP BGG was abolished by a selecting injection of the homologous conjugate. The response was depressed to a smaller degree by injections of either BGG or dinitrophenylated human serum albumin, suggesting that carrier-specific (T) and hapten-specific (B) lymphocytes could be separately selected from the recirculating pool. The regional selection of recirculating lymphocytes by antigen may explain a number of phenomena in which the prior injection of antigen has been found to inhibit a subsequent immune response.

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Selected References

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  1. Asherson G. L. Selective and specific inhibition of 24-hour skin reactions in the guinea-pig. II. The mechanism of immune deviation. Immunology. 1966 Feb;10(2):179–186. [PMC free article] [PubMed] [Google Scholar]
  2. Axelrad M., Rowley D. A. Hypersensitivity: specific immunologic suppression of the delayed type. Science. 1968 Jun 28;160(3835):1465–1467. doi: 10.1126/science.160.3835.1465. [DOI] [PubMed] [Google Scholar]
  3. Ellis S. T., Gowans J. L., Howard J. C. The origin of antibody forming cells from lymphocytes. Antibiot Chemother. 1969;15:40–55. doi: 10.1159/000386770. [DOI] [PubMed] [Google Scholar]
  4. Feldbush T. L., Gowans J. L. Antigen modulation of the immune response. The effect of delayed challenge on the affinity of anti-dinitrophenylated bovine gamma globulin antibody produced in adoptive recipients. J Exp Med. 1971 Dec 1;134(6):1453–1465. doi: 10.1084/jem.134.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ford W. L., Atkins R. C. Specific unresponsiveness of recirculating lymphocytes ater exposure to histocompatibility antigen in F 1 hybrid rats. Nat New Biol. 1971 Dec 8;234(49):178–180. doi: 10.1038/newbio234178a0. [DOI] [PubMed] [Google Scholar]
  6. Ford W. L., Burr W., Simonsen M. A lymph node weight assay for the graft-versus-host activity of rat lymphoid cells. Transplantation. 1970 Sep;10(3):258–266. doi: 10.1097/00007890-197009000-00007. [DOI] [PubMed] [Google Scholar]
  7. Ford W. L., Gowans J. L. The role of lymphocytes in antibody formation. II. The influence of lymphocyte migration on the initiation of antibody formation in the isolated, perfused spleen. Proc R Soc Lond B Biol Sci. 1967 Sep 12;168(1012):244–262. doi: 10.1098/rspb.1967.0064. [DOI] [PubMed] [Google Scholar]
  8. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  9. GOWANS J. L. The fate of parental strain small lymphocytes in F1 hybrid rats. Ann N Y Acad Sci. 1962 Oct 24;99:432–455. doi: 10.1111/j.1749-6632.1962.tb45326.x. [DOI] [PubMed] [Google Scholar]
  10. Gowans J. L. Life-span, recirculation, and transformation of lymphocytes. Int Rev Exp Pathol. 1966;5:1–24. [PubMed] [Google Scholar]
  11. Gowans J. L. Lymphocytes. Harvey Lect. 1968 1969;64:87–119. [PubMed] [Google Scholar]
  12. Hall J. G., Morris B. The immediate effect of antigens on the cell output of a lymph node. Br J Exp Pathol. 1965 Aug;46(4):450–454. [PMC free article] [PubMed] [Google Scholar]
  13. Howard J. C., Hunt S. V., Gowans J. L. Identification of marrow-derived and thymus-derived small lymphocytes in the lymphoid tissue and thoracic duct lymph of normal rats. J Exp Med. 1972 Feb 1;135(2):200–219. doi: 10.1084/jem.135.2.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Howard J. C. The life-span and recirculation of marrow-derived small lymphocytes from the rat thoracic duct. J Exp Med. 1972 Feb 1;135(2):185–199. doi: 10.1084/jem.135.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jerne N. K., Nordin A. A. Plaque Formation in Agar by Single Antibody-Producing Cells. Science. 1963 Apr 26;140(3565):405–405. doi: 10.1126/science.140.3565.405. [DOI] [PubMed] [Google Scholar]
  16. Macher E., Chase M. W. Studies on the sensitization of animals with simple chemical compounds. XII. The influence of excision of allergenic depots on onset of delayed hypersensitivity and tolerance. J Exp Med. 1969 Jan 1;129(1):103–121. doi: 10.1084/jem.129.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McGregor D. D., McCullagh P. J., Gowans J. L. The role of lymphocytes in antibody formation. I. Restoration of the haemolysin response in x-irradiated rats with lymphocytes from normal and immunologically tolerant donors. Proc R Soc Lond B Biol Sci. 1967 Sep 12;168(1012):229–243. doi: 10.1098/rspb.1967.0063. [DOI] [PubMed] [Google Scholar]
  18. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol. 1971 Jan;1(1):18–27. doi: 10.1002/eji.1830010104. [DOI] [PubMed] [Google Scholar]
  19. NEIDERS M. E., ROWLEY D. A., FITCH F. W. The sustained suppression of hemolysin response in passively immunized rats. J Immunol. 1962 Jun;88:718–724. [PubMed] [Google Scholar]
  20. O'Toole C. M., Davies A. J. Pre-emption in immunity. Nature. 1971 Mar 19;230(5290):187–189. doi: 10.1038/230187a0. [DOI] [PubMed] [Google Scholar]
  21. ROWLEY D. A., FITCH F. W. HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT. J Exp Med. 1964 Dec 1;120:987–1005. doi: 10.1084/jem.120.6.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rowley D. A., Fitch F. W., Axelrad M. A., Pierce C. W. The immune response suppressed by specific antibody. Immunology. 1969 Apr;16(4):549–559. [PMC free article] [PubMed] [Google Scholar]
  23. Schlossman S. F., Levin H. A., Rocklin R. E., David J. R. The compartmentalization of antigen-reactive lymphocytes in desensitized guinea pigs. J Exp Med. 1971 Sep 1;134(3 Pt 1):741–750. doi: 10.1084/jem.134.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sprent J., Miller J. F., Mitchell G. F. Antigen-induced selective recruitment of circulating lymphocytes. Cell Immunol. 1971 Apr;2(2):171–181. doi: 10.1016/0008-8749(71)90036-0. [DOI] [PubMed] [Google Scholar]
  25. Stuart F. P., Saitoh T., Fitch F. W. Rejection of renal allografts: specific immunologic suppression. Science. 1968 Jun 28;160(3835):1463–1465. doi: 10.1126/science.160.3835.1463. [DOI] [PubMed] [Google Scholar]
  26. Wigzell H. Specific fractionation of immunocompetent cells. Transplant Rev. 1970;5:76–104. doi: 10.1111/j.1600-065x.1970.tb00357.x. [DOI] [PubMed] [Google Scholar]