Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1975 Dec 1;142(6):1550–1563. doi: 10.1084/jem.142.6.1550

Cellular kinetics of the intestinal immune response to cholera toxoid in rats

PMCID: PMC2190063  PMID: 1238506

Abstract

The aims of this study were (a) to find a regime of immunization with cholera toxoid in rats which would establish a high density of antitoxin containing cells (ACC) in the lamina propria of the intestine and (b) to determine the origin of the ACC. The best cellular response was achieved by a single i.p. dose of toxoid in FCA followed by an intraintestinal boost 2 wk later. ACC appeared in the thoracic duct lymph 2 days after boosting, reaching a peak of about 200,000 ACC/h at 3--4 days. This was followed by the appearance of large numbers of ACC in the intestine. The i.p. dose of toxoid by itself gave rise to very few ACC in the gut or thoracic duct lymph, but it had clearly primed the gut immune system for a secondary response. Priming was also achieved by the prolonged oral intake of toxoid. The importance of the intestinal route for boosting was shown by the failure of i.p. challenge to give an ACC response in the intestine after i.p. priming and the small response it provoked after oral priming. ACC among thoracic duct lymphocytes (TDL) and in the lamina propria contained predominantly IgA. Two observations indicated that the major source of the lamina propria ACC was from cells that emerged in the thoracic duct lymph after intraintestinal challenge. Firstly, the establishment of a thoracic duct fistula immediately before challenge prevented the appearance of ACC in the intestine. Secondly, many ACC appeared in the intestine of normal rats after the injection of TDL rich in ACC. Although homing of ACC precursors to the gut was not antigen-dependent, the distribution of ACC in the lamina propria was considerably influenced by the site of the intestinal challenge, the density of ACC being greatest at or distal to the site of injection of toxoid into the lumen of the gut.

Full Text

The Full Text of this article is available as a PDF (830.4 KB).

Selected References

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

  1. Beh K. J., Lascelles A. K. Class specificity of intracellular and surface immunoglobulin of cells in popliteal and intestinal lymph from sheep. Aust J Exp Biol Med Sci. 1974 Jun;52(Pt 3):505–514. doi: 10.1038/icb.1974.49. [DOI] [PubMed] [Google Scholar]
  2. Bienenstock J., Dolezel J. Peyer's patches: lack of specific antibody-containing cells after oral and parenteral immunization. J Immunol. 1971 Apr;106(4):938–945. [PubMed] [Google Scholar]
  3. Craig J. P., Eichner E. R., Hornick R. B. Cutaneous responses to cholera skin toxin in man. I. Responses in unimmunized American males. J Infect Dis. 1972 Mar;125(3):203–215. doi: 10.1093/infdis/125.3.203. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Griscelli C., Vassalli P., McCluskey R. T. The distribution of large dividing lymph node cells in syngeneic recipient rats after intravenous injection. J Exp Med. 1969 Dec 1;130(6):1427–1451. doi: 10.1084/jem.130.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Guy-Grand D., Griscelli C., Vassalli P. The gut-associated lymphoid system: nature and properties of the large dividing cells. Eur J Immunol. 1974 Jun;4(6):435–443. doi: 10.1002/eji.1830040610. [DOI] [PubMed] [Google Scholar]
  7. HALL J. G., MORRIS B. The lymph-borne cells of the immune response. Q J Exp Physiol Cogn Med Sci. 1963 Jul;48:235–247. doi: 10.1113/expphysiol.1963.sp001660. [DOI] [PubMed] [Google Scholar]
  8. Hall J. G., Parry D. M., Smith M. E. The distribution and differentiation of lymph-borne immunoblasts after intravenous injection into syngeneic recipients. Cell Tissue Kinet. 1972 May;5(3):269–281. doi: 10.1111/j.1365-2184.1972.tb00365.x. [DOI] [PubMed] [Google Scholar]
  9. Halstead T. E., Hall J. G. The homing of lymph-borne immunoblasts to the small gut of neonatal rats. Transplantation. 1972 Sep;14(3):339–346. doi: 10.1097/00007890-197209000-00009. [DOI] [PubMed] [Google Scholar]
  10. Hochstein H. D., Feeley J. C., DeWitt W. E. Titration of cholera antitoxin in human sera by microhemagglutination with formalinized erythrocytes. Appl Microbiol. 1970 May;19(5):742–745. doi: 10.1128/am.19.5.742-745.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jensenius J. C., Williams A. F. The binding of anti-immunoglobulin antibodies to rat thymocytes and thoracic duct lymphocytes. Eur J Immunol. 1974 Feb;4(2):91–97. doi: 10.1002/eji.1830040207. [DOI] [PubMed] [Google Scholar]
  12. Jensenius J. C., Williams A. F. Total immunoglobulin of rat thymocytes and thoracic duct lymphocytes. Eur J Immunol. 1974 Feb;4(2):98–105. doi: 10.1002/eji.1830040208. [DOI] [PubMed] [Google Scholar]
  13. Newcomb R. W., Ishizaka K., DeVald B. L. Human IgG and IgA diphtheria antitoxins in serum, nasal fluids and saliva. J Immunol. 1969 Aug;103(2):215–224. [PubMed] [Google Scholar]
  14. Parrott D. M., Ferguson A. Selective migration of lymphocytes within the mouse small intestine. Immunology. 1974 Mar;26(3):571–588. [PMC free article] [PubMed] [Google Scholar]
  15. Pierce N. F., Reynolds H. Y. Immunity to experimental cholera. I. Protective effect of humoral IgG antitoxin demonstrated by passive immunization. J Immunol. 1974 Sep;113(3):1017–1023. [PubMed] [Google Scholar]
  16. The T. H., Feltkamp T. E. Conjugation of fluorescein isothiocyanate to antibodies. I. Experiments on the conditions of conjugation. Immunology. 1970 Jun;18(6):865–873. [PMC free article] [PubMed] [Google Scholar]
  17. Williams A. F., Gowans J. L. The presence of IgA on the surface of rat thoractic duct lymphocytes which contain internal IgA. J Exp Med. 1975 Feb 1;141(2):335–345. doi: 10.1084/jem.141.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES