Cargando…

AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS

The epidermolytic syndrome that can be obtained at will in F(1) hybrid hamsters by the cutaneous inoculation of adequate doses of parental strain lymphoid cells has been investigated to determine whether the cutaneous lesions are due to an autoimmune process arising from the severe, initial GVH reac...

Descripción completa

Detalles Bibliográficos
Autores principales: Streilein, J. Wayne, Billingham, R. E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1970
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2138749/
https://www.ncbi.nlm.nih.gov/pubmed/4396297
_version_ 1782143635712638976
author Streilein, J. Wayne
Billingham, R. E.
author_facet Streilein, J. Wayne
Billingham, R. E.
author_sort Streilein, J. Wayne
collection PubMed
description The epidermolytic syndrome that can be obtained at will in F(1) hybrid hamsters by the cutaneous inoculation of adequate doses of parental strain lymphoid cells has been investigated to determine whether the cutaneous lesions are due to an autoimmune process arising from the severe, initial GVH reactions in the skin. It was amply demonstrated that inoculation of donor cells into the skin was of crucial importance to the development of epidermolysis. Parental strain lymphoid cells in similar doses delivered by any other route into normal F(1) hybrids failed absolutely to incite the acute syndrome. If "immune lymphocyte transfer" reactions incited by donor cells in the host's skin were surgically removed at timed intervals after inoculation, only complete excision within 24 hr prevented the appearance of epidermolysis in F(1) hybrid hosts, indicating that inoculated donor cells must remain within the confines of the skin for approximately 24 hr in order to evoke the disease, persistence for longer periods of time being unnecessary for the subsequent course of the disease. However, reconstitution experiments involving the intramuscular inoculation of suspensions containing mixtures of donor cells and host lymphoid cells, in the presence or absence of epidermal cells, unequivocally indicated that no intimate exposure of lymphoid cells to putative skin-specific antigens was essential. Similarly, the elicitation of generalized epidermolysis in F(1) hybrids irradiated with 300 r and then inoculated intravenously with donor cells casts further doubt on the pathogenic importance of the skin as a source of tissue-specific antigen. The results of subsequent experiments indicated that host leukocytes, rather than parenchymal cells of the dermis or the epidermis, were important contributors of the transplantation antigenic stimulus. Moreover, a series of experiments, using (CB x MHA)F(1) hybrid hosts that had been lethally irradiated and reconstituted with bone marrow cells from ALS-treated MHA donors, indicated that from 6 to 10 wk after reconstitution—when direct and immune lymphocyte transfer reactions showed a virtual absence of native F(1) leukocytes from the circulation—donor cells obtained from specifically sensitized MHA donors were completely ineffective in inducing epidermolysis, while equivalent lymphoid cell inocula derived from CB donors evoked the cutaneous disease irrespective of the time elapsed since reconstitution. To explain these findings it is postulated that in hamsters, the primary targets in graft-versus-host disease incited by the intracutaneous inoculation of donor cells are leukocytes originating in bone marrow or lymph node, or both.
format Text
id pubmed-2138749
institution National Center for Biotechnology Information
language English
publishDate 1970
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21387492008-04-17 AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS Streilein, J. Wayne Billingham, R. E. J Exp Med Article The epidermolytic syndrome that can be obtained at will in F(1) hybrid hamsters by the cutaneous inoculation of adequate doses of parental strain lymphoid cells has been investigated to determine whether the cutaneous lesions are due to an autoimmune process arising from the severe, initial GVH reactions in the skin. It was amply demonstrated that inoculation of donor cells into the skin was of crucial importance to the development of epidermolysis. Parental strain lymphoid cells in similar doses delivered by any other route into normal F(1) hybrids failed absolutely to incite the acute syndrome. If "immune lymphocyte transfer" reactions incited by donor cells in the host's skin were surgically removed at timed intervals after inoculation, only complete excision within 24 hr prevented the appearance of epidermolysis in F(1) hybrid hosts, indicating that inoculated donor cells must remain within the confines of the skin for approximately 24 hr in order to evoke the disease, persistence for longer periods of time being unnecessary for the subsequent course of the disease. However, reconstitution experiments involving the intramuscular inoculation of suspensions containing mixtures of donor cells and host lymphoid cells, in the presence or absence of epidermal cells, unequivocally indicated that no intimate exposure of lymphoid cells to putative skin-specific antigens was essential. Similarly, the elicitation of generalized epidermolysis in F(1) hybrids irradiated with 300 r and then inoculated intravenously with donor cells casts further doubt on the pathogenic importance of the skin as a source of tissue-specific antigen. The results of subsequent experiments indicated that host leukocytes, rather than parenchymal cells of the dermis or the epidermis, were important contributors of the transplantation antigenic stimulus. Moreover, a series of experiments, using (CB x MHA)F(1) hybrid hosts that had been lethally irradiated and reconstituted with bone marrow cells from ALS-treated MHA donors, indicated that from 6 to 10 wk after reconstitution—when direct and immune lymphocyte transfer reactions showed a virtual absence of native F(1) leukocytes from the circulation—donor cells obtained from specifically sensitized MHA donors were completely ineffective in inducing epidermolysis, while equivalent lymphoid cell inocula derived from CB donors evoked the cutaneous disease irrespective of the time elapsed since reconstitution. To explain these findings it is postulated that in hamsters, the primary targets in graft-versus-host disease incited by the intracutaneous inoculation of donor cells are leukocytes originating in bone marrow or lymph node, or both. The Rockefeller University Press 1970-07-01 /pmc/articles/PMC2138749/ /pubmed/4396297 Text en Copyright © 1970 by The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Streilein, J. Wayne
Billingham, R. E.
AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS
title AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS
title_full AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS
title_fullStr AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS
title_full_unstemmed AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS
title_short AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS : II. THE EPIDERMOLYTIC SYNDROME: STUDIES ON ITS PATHOGENESIS
title_sort analysis of graft-versus-host disease in syrian hamsters : ii. the epidermolytic syndrome: studies on its pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2138749/
https://www.ncbi.nlm.nih.gov/pubmed/4396297
work_keys_str_mv AT streileinjwayne ananalysisofgraftversushostdiseaseinsyrianhamstersiitheepidermolyticsyndromestudiesonitspathogenesis
AT billinghamre ananalysisofgraftversushostdiseaseinsyrianhamstersiitheepidermolyticsyndromestudiesonitspathogenesis
AT streileinjwayne analysisofgraftversushostdiseaseinsyrianhamstersiitheepidermolyticsyndromestudiesonitspathogenesis
AT billinghamre analysisofgraftversushostdiseaseinsyrianhamstersiitheepidermolyticsyndromestudiesonitspathogenesis