Pathogenesis of the Graft-Versus-Host Reagtion in Chicken Embryos. Requirement of Yolk Sac-Derived Stem Cells for the Development of Proliferative Lesions

Abstract

Summary. Randomly bred chicken enibr>os were inoculated on days 5, 6 and 10 witb adult .\A blood and examined on day 13. Widespread haemorrhages oceurred on the body surface, the yolk sac was poorly developed and haemopoietic tissue of the yolk sac fokl.s was severely dt-pletiid. Lymphopoiesi.s in the tliymn.s was depressed and tlie difFerintintion of the l)irrsa of Fabricius was retirded. Tliese lesioiw are characteri.stic of a graft-versus-host reaction in very young (rather tlian l()-day-old) embryos and appear to result from the ilestniction of haemopoictic stem cells in the yolk sac thus preventing their dissemination to intra-cmbr>onic baemopoietk-organs.Since it has been suggested that yolk sac-derived stem cells are required for the development of proliferative lesions during a graft-versus-host reaction in oUlcr rmhryos, tlic pock-forming ability of these embryos depleted of stem cells by an early graft-\crsus-host reaction was examined. Randomly bred embryos inoculated on days o and 6 tleveloped very few jwcks in response to a third inoculation of adnlt AA hlood on day 10. In comparison. AA cliicken embryo.s inocnlated ou da\s .5 and fi witli adult .W blcK)d Iwfore inoculation oT adult allof:;eneic blond onto the dioridnllantoic inenihrane on ilay 10 developed nonnal numbcr.s uf pocks. Tliese results support the hypotliesis that yolk sac-derived stem cells are required for the development of proliferative lesions during a gnift-versus-host reaction.

Cellular basis of graft‐versus‐host reactions

“…Murphy believed that splenomegaly resulted from stimulation of host spleen cells by the inoculum, subsequent proliferation of host lymphocytes in the spleen, and migration of splenic lymphocytes to various sites in the membranes. It is now known that the nodules resulted from grafted lymphoid cells reacting to foreign histocompatibility antigens present on host lymphoid cells and consist of proliferating donor as well as host cells (Gowans, 1968;Walker et al, 1973. ) It was not until 40 years after Murphy's observation that investigators began to analyze specific mechanisms of the GVHR.…”

“…They interpreted runt disease as resulting from an immunological attack by the injected spleen cells on the immunologically immature recipient. It has subsequently been shown that runt disease is really a secondary disease or graft-versus-host disease (GVHD) resulting from an immunologic response of mature donor T cells carried in the graft to foreign histocompatibility major and minor alloantigens (Gowans, 1968;Boehmer and Sprent, 1976;Korngold and Sprent, 1978) presented to them in an immunogenic form by host lymphohematopoietic (Elkins, 1971a;Walker et al, 1973;Ahmann et al, 1979) or dendritic (Steinman and Witmer, 1978) cells. However, it should be pointed out that recent evidence indicates that T cells causing GVHD to minor (i.e., mouse non-H-2) alloantigens are induced at the level of marrowderived cells and then, at the effector phase, cause lethal GVHD by attacking minor histocompatibility antigen-bearing nonhematopoietic cells (Korngold and Sprent, 1982).…”

Allogeneic Interactions Provide Evidence for a Novel Class of Immunological Reactivity

“…Further experimental findings support this suggestion. When a GVH reaction is initiated at a very early stage of embryonic life and dissemination of stem cells from the yolk sac is prevented, the embryo is later unable to develop proliferative lesions when adult allogeneic blood is introduced onto tbe CAM (Walker et al 1972c).…”