Abstract
We investigated the traffic of allograft-responding leukocytes between the host and graft without handling of these cells in vitro. The blood flow between the host and graft was disconnected, the proliferating cells were labeled with [3H]thymidine selectively in the graft or in the host, the label was chased with cold thymidine, and the circulation was reestablished. The localization of labeled cells was quantitated by autoradiography. The first host-derived labeled cells appeared in the graft and graft-derived labeled cells in the host, already on the 1st d after transplantation. This was followed by an exponential increase in the labeled cell traffic in both directions. The peak of traffic was observed on day 4 after transplantation, whereafter the traffic rapidly declined and tapered off. This decline was not due to exhaustion of supply, as the labeled cells continued to proliferate in their original compartments, nor to a slowdown of blood circulation, which took place 2-3 d later. We consider the decline to indicate that the rejection has proceeded to a (irreversible) stage autonomous of the host lymphatic and hematopoietic system. During the exponential increase, nearly one- third of the graft-infiltrating inflammatory cells were replaced as a consequence of relocalization during each 18-h-period. All mononuclear white cell types, with the exception of granulocytes, participated in the traffic. Most lymphoid cells entrapped in the graft were descendents of recent cell divisions; most of the mononuclear phagocytes derived from a preexisting phagocyte pool. The entrapment of labeled leukocytes in a relevant graft was specific: when an allograft and an autograft were simultaneously transplanted, a more than 50-fold entrapment was observed in the allograft, compared with the autograft. Very few of the cells localized in irrelevant positions, such as the liver and lung, of the recipient.
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Selected References
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- Ascher N. L., Chen S., Hoffman R., Simmons R. L. Maturation of cytotoxic effector cells at the site of allograft rejection. Transplant Proc. 1981 Mar;13(1 Pt 2):1105–1107. [PubMed] [Google Scholar]
- Bergman G., Husberg B. A method for multiple intraarterial injections in the allogeneic or isogeneic transplanted rat kidney by use of a long term catheter in the renal artery. Scand J Urol Nephrol Suppl. 1980;54:116–119. [PubMed] [Google Scholar]
- Binz H., Wigzell H., Häyry P. Correlation between specific cytolysis and expression of idiotypic receptors of allograft-infiltrating cells. Nature. 1976 Feb 5;259(5542):401–403. doi: 10.1038/259401a0. [DOI] [PubMed] [Google Scholar]
- Chang A. E., Sugarbaker P. H. Preferential homing of passively transferred T cells into skin allografts of mice. Transplantation. 1979 Sep;28(3):247–252. doi: 10.1097/00007890-197909000-00018. [DOI] [PubMed] [Google Scholar]
- Chang A. E., Sugarbaker P. H. Preferential homing of passively transferred T cells into skin allografts of mice. Transplantation. 1979 Sep;28(3):247–252. doi: 10.1097/00007890-197909000-00018. [DOI] [PubMed] [Google Scholar]
- Emeson E. E. Migratory behavior of lymphocytes with specific reactivity to alloantigens. II. Selective recruitment to lymphoid cell allografts and their draining lymph nodes. J Exp Med. 1978 Jan 1;147(1):13–24. doi: 10.1084/jem.147.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ford W. L. Lymphocyte migration and immune responses. Prog Allergy. 1975;19:1–59. doi: 10.1159/000313381. [DOI] [PubMed] [Google Scholar]
- GOWANS J. L. THE ROLE OF LYMPHOCYTES IN THE DESTRUCTION OF HOMOGRAFTS. Br Med Bull. 1965 May;21:106–110. doi: 10.1093/oxfordjournals.bmb.a070376. [DOI] [PubMed] [Google Scholar]
- Hall J. G. Studies of the cells in the afferent and efferent lymph of lymph nodes draining the site of skin homografts. J Exp Med. 1967 May 1;125(5):737–754. doi: 10.1084/jem.125.5.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamburger J., Dimitriu A., Bankir L., Debray-Sachs M., Auvert J. Collection of lymph from kidneys homotransplanted in man: cell transformation in vivo. Nature. 1971 Aug 27;232(5313):633–634. doi: 10.1038/232633a0. [DOI] [PubMed] [Google Scholar]
- Hay J. B., Hobbs B. B. The flow of blood to lymph nodes and its relation to lymphocyte traffic and the immune response. J Exp Med. 1977 Jan 1;145(1):31–44. doi: 10.1084/jem.145.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Häyry P., von Willebrand E. Practical guidelines for fine needle aspiration biopsy of human renal allografts. Ann Clin Res. 1981;13(4-5):288–306. [PubMed] [Google Scholar]
- Issekutz T. B., Chin W., Hay J. B. Lymphocyte traffic through granulomas: differences in the recovery of indium-111-labeled lymphocytes in afferent and efferent lymph. Cell Immunol. 1980 Aug 15;54(1):79–86. doi: 10.1016/0008-8749(80)90191-4. [DOI] [PubMed] [Google Scholar]
- Lance E. M., Cooper S. Homing of specifically sensitized lymphocytes to allografts of skin. Cell Immunol. 1972 Sep;5(1):66–73. doi: 10.1016/0008-8749(72)90084-6. [DOI] [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]
- PRENDERGAST R. A. CELLULAR SPECIFICITY IN THE HOMOGRAFT REACTION. J Exp Med. 1964 Mar 1;119:377–388. doi: 10.1084/jem.119.3.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen N. C., Morris B. The role of the lymphatic system in the rejection of homografts: a study of lymph from renal transplants. J Exp Med. 1970 May 1;131(5):936–969. doi: 10.1084/jem.131.5.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roberts P. J., Häyry P. Effector mechanisms in allograft rejection. II. Density, electrophoresis, and size fractionation of allograft-infiltrating cells demonstrating several classes of killer cells. Cell Immunol. 1977 May;30(2):236–253. doi: 10.1016/0008-8749(77)90068-5. [DOI] [PubMed] [Google Scholar]
- Sprent J., Miller J. F. Fate of H2-activated T lymphocytes in syngeneic hosts. II. Residence in recirculating lymphocyte pool and capacity to migrate to allografts. Cell Immunol. 1976 Feb;21(2):303–313. doi: 10.1016/0008-8749(76)90058-7. [DOI] [PubMed] [Google Scholar]
- Tilney N. L., Ford W. L. The migration of rat lymphoid cells into skin grafts. Some sensitised cells localise preferentially in specific allografts. Transplantation. 1974 Jan 1;17(1):12–21. doi: 10.1097/00007890-197401000-00004. [DOI] [PubMed] [Google Scholar]
- Tilney N. L., Notis-McConarty J., Strom T. B. Specificity of cellular migration into cardiac allografts in rats. Transplantation. 1978 Sep;26(3):181–186. doi: 10.1097/00007890-197809000-00011. [DOI] [PubMed] [Google Scholar]
- Tilney N. L., Strom T. B., Macpherson S. G., Carpenter C. B. Surface properties and functional characteristics of infiltrating cells harvested from acutely rejecting cardiac allografts in inbred rats. Transplantation. 1975 Oct;20(4):323–330. doi: 10.1097/00007890-197510000-00009. [DOI] [PubMed] [Google Scholar]
- Woodruff J. J., Gesner B. M. The effect of neuraminidase on the fate of transfused lymphocytes. J Exp Med. 1969 Mar 1;129(3):551–567. doi: 10.1084/jem.129.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Willebrand E., Soots A., Häyry P. In situ effector mechanisms in rat kidney allograft rejection. I. Characterization of the host cellular infiltrate in rejecting allograft parenchyma. Cell Immunol. 1979 Sep 1;46(2):309–326. doi: 10.1016/0008-8749(79)90419-2. [DOI] [PubMed] [Google Scholar]
- von Willebrand E., Soots A., Häyry P. In situ effector mechanisms in rat kidney allograft rejection. II. Heterogeneity of the effector cells in the inflammatory infiltrate vs that in the spleen of the recipient rat. Cell Immunol. 1979 Sep 1;46(2):327–336. doi: 10.1016/0008-8749(79)90420-9. [DOI] [PubMed] [Google Scholar]
