Abstract
Mice or rats that have been rendered tolerant of skin homografts from an alien donor strain furnish the basis of a very sensitive and objective test system for investigating the competence of cellular inocula from specifically immunized isologous donors to transfer sensitivity adoptively. By means of this test system it has been shown that immunologically "activated" cells, capable of transferring homograft sensitivity, are present in the blood, peritoneal exudates, and regional nodes of animals that have rejected skin homografts. Leucocytes were as effective as regional node cells. Activated cells were first demonstrable in the regional nodes and blood of skin homograft recipients at the same time,—on the 6th postoperative day,—suggesting that these cells must enter the circulation very soon after their formation in the nodes. Moreover, when sensitization was effected by skin homografts, but not by means of splenic cell suspensions inoculated intraperitoneally, activated cells are highly persistent, still being demonstrable in both the blood and the nodes more than a year after sensitization. The finding that thoracic duct cells, which are almost exclusively lymphocytes, were just as effective as leucocytes or regional nodes in transferring sensitivity in rats formally identifies the cell type responsible for transferring sensitivity in the various tissues tested. Attempts to transfer sensitivity to homografts in normal mice or tolerant mice by means of larger dosages of activated lymphoid cells sequestered in Millipore chambers inserted intraperitoneally were unsuccessful. All this, and other evidence presented, lends strength to the thesis that skin homograft immunity is a cell-mediated reaction.
Full Text
The Full Text of this article is available as a PDF (1.3 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ANDERSON N. F., DELORME E. J., WOODRUFF M. F. Induction of runt disease in rats by injection of thoracic duct lymphocytes at birth. Transplant Bull. 1960 Jan;7:93–97. doi: 10.1097/00006534-196001000-00033. [DOI] [PubMed] [Google Scholar]
- BILLINGHAM R. E., BRENT L., BROWN J. B., MEDAWAR P. B. Time of onset and duration of transplantation immunity. Transplant Bull. 1959 Oct;6:410–414. doi: 10.1097/00006534-195910000-00035. [DOI] [PubMed] [Google Scholar]
- BILLINGHAM R. E., BRENT L. Further attempts to transfer transplantation immunity by means of serum. Br J Exp Pathol. 1956 Dec;37(6):566–569. [PMC free article] [PubMed] [Google Scholar]
- BILLINGHAM R. E., BROWN J. B., DEFENDI V., SILVERS W. K., STEINMULLER D. Quantitative studies on the induction of tolerance of homologous tissues and on runt disease in the rat. Ann N Y Acad Sci. 1960 May 31;87:457–471. doi: 10.1111/j.1749-6632.1960.tb23213.x. [DOI] [PubMed] [Google Scholar]
- BILLINGHAM R. E., DEFENDIV, SILVERS W. K., STEINMULLER D. Quantitative studies on the induction of tolerance of skin homografts and on runt disease in neonatal rats. J Natl Cancer Inst. 1962 Feb;28:365–435. [PubMed] [Google Scholar]
- BILLINGHAM R. E., SILVERS W. K. Quantitative studies on the ability of cells of different origins to induce tolerance of skin homografts and cause runt disease in neonatal mice. J Exp Zool. 1961 Mar;146:113–129. doi: 10.1002/jez.1401460202. [DOI] [PubMed] [Google Scholar]
- BILLINGHAM R. E., SILVERS W. K., WILSON D. B. Adoptive transfer of transplantation immunity by means of blood-borne cells. Lancet. 1962 Mar 10;1(7228):512–515. doi: 10.1016/s0140-6736(62)91484-8. [DOI] [PubMed] [Google Scholar]
- DUNN T. B. Normal and pathologic anatomy of the reticular tissue in laboratory mice, with a classification and discussion of neoplasms. J Natl Cancer Inst. 1954 Jun;14(6):1281–1433. [PubMed] [Google Scholar]
- FALLS N. G., KIRSCHBAUM A. Passive immunization of mice in parabiosis against a transplanted lymphosarcoma. Cancer Res. 1953 Oct;13(10):741–743. [PubMed] [Google Scholar]
- GOWANS J. L., McGREGOR D. D., COWEN D. M. Initiation of immune responses by small lymphocytes. Nature. 1962 Nov 17;196:651–655. doi: 10.1038/196651a0. [DOI] [PubMed] [Google Scholar]
- GOWANS J. L. The effect of the continuous re-infusion of lymph and lymphocytes on the output of lymphocytes from the thoracic duct of unanaesthetized rats. Br J Exp Pathol. 1957 Feb;38(1):67–78. [PMC free article] [PubMed] [Google Scholar]
- 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]
- GOWANS J. L. The recirculation of lymphocytes from blood to lymph in the rat. J Physiol. 1959 Apr 23;146(1):54–69. doi: 10.1113/jphysiol.1959.sp006177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HASKOVA V., MITCHISON N. A. Migration of spleen cells from subcutaneous implantation sites. Nature. 1958 Aug 9;182(4632):410–410. doi: 10.1038/182410a0. [DOI] [PubMed] [Google Scholar]
- KRETSCHMER R. R., PEREZ-TAMAYO R. The role of humoral antibodies in rejection of skin homografts in rabbits. II. Passive transfer of transplantation immunity by sensitized lymph node cells within diffusion chambers. J Exp Med. 1962 Dec 1;116:879–896. doi: 10.1084/jem.116.6.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KROHN P. L., ZUCKERMAN A. The effect of splenectomy on the survival of skin homografts in rabbits and on the response to cortisone. Br J Exp Pathol. 1954 Jun;35(3):223–226. [PMC free article] [PubMed] [Google Scholar]
- MCCLUSKEY R. T., BENACERRAF B., MCCLUSKEY J. W. STUDIES ON THE SPECIFICITY OF THE CELLULAR INFILTRATE IN DELAYED HYPERSENSITIVITY REACTIONS. J Immunol. 1963 Mar;90:466–477. [PubMed] [Google Scholar]
- MEDAWAR P. B. The homograft reaction. Proc R Soc Lond B Biol Sci. 1958 Dec 4;149(935):145–166. doi: 10.1098/rspb.1958.0058. [DOI] [PubMed] [Google Scholar]
- MITCHISON N. A. Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer. J Exp Med. 1955 Aug 1;102(2):157–177. doi: 10.1084/jem.102.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NAJARIAN J. S., FELDMAN J. D. Passive transfer of transplantation immunity. I. Tritiated lymphoid cells. II. Lymphoid cells in millipore chambers. J Exp Med. 1962 May 1;115:1083–1093. doi: 10.1084/jem.115.5.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NAJARIAN J. S. Mechanism of homograft rejection. Plast Reconstr Surg Transplant Bull. 1962 Sep;30:359–367. doi: 10.1097/00006534-196209000-00006. [DOI] [PubMed] [Google Scholar]
- PATERSON P. Y., DIDAKOW N. C. Transfer of allergic encephalomyelitis using splenectomized albino rats. Proc Soc Exp Biol Med. 1961 Dec;108:768–771. doi: 10.3181/00379727-108-27061. [DOI] [PubMed] [Google Scholar]
- PORTER K. A., CALNE R. Y. Origin of the infiltrating cells in skin and kidney homografts. Transplant Bull. 1960 Oct;26:458–464. doi: 10.1097/00006534-196010000-00041. [DOI] [PubMed] [Google Scholar]
- ROSENAU W., MOON H. D. Lysis of homologous cells by sensitized lymphocytes in tissue culture. J Natl Cancer Inst. 1961 Aug;27:471–483. [PubMed] [Google Scholar]
- SCOTHORNE R. J. Lymphatic repair and the genesis of homograft immunity. Ann N Y Acad Sci. 1958 Oct 7;73(3):673–675. doi: 10.1111/j.1749-6632.1959.tb40843.x. [DOI] [PubMed] [Google Scholar]
- SCOTHORNE R. J., MCGREGOR I. A. Cellular changes in lymph nodes and spleen following skin homografting in the rabbit. J Anat. 1955 Jul;89(3):283–292. [PMC free article] [PubMed] [Google Scholar]
- TERASAKI P. I. Identification of the type of blood-cell responsible for the graft-versus-host reaction in chicks. J Embryol Exp Morphol. 1959 Sep;7:394–408. [PubMed] [Google Scholar]
- WINN H. J. Immune mechanisms in homotransplantation. II. Quantitative assay of the immunologic activity of lymphoid cells stimulated by tumor homografts. J Immunol. 1961 Feb;86:228–239. [PubMed] [Google Scholar]
- WINN H. J. The immune response and the homograft reaction. Natl Cancer Inst Monogr. 1960 Mar;2:113–138. [PubMed] [Google Scholar]