Nonspecific Cytotoxicity in Graft-Versus-Host Reactions

Singh, Jagat N.; Sabbadini, E; Sehon, A.H.

doi:10.1097/00007890-197105000-00008

Cited by 12 publications

(6 citation statements)

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“…But the exposure of lymphocytes to H O S T CELL R E S P O N S E I N K I D N E Y allogeneic antigens is said to result in a specific (6,21) cytotoxic activity. Other evidence, however, indicates that such specifically stimulated lymphocytes can also launch a nonspecific attack on target tissues (22)(23)(24)(25)(26). Tissue destruction in the renal GVH reaction is clearly nonspecific, as reported by others (4,12) and confirmed in the present studies by inducing renal damage with Lew TDL in immunologically unresponsive Lew hosts whose nucleated white blood cells were derived from L/BN bone marrow.…”

Section: The E2fect Of Mixing Defined Populations Of Parental and Fi supporting

confidence: 84%

THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES

Volkman

1972

The Journal of Experimental Medicine

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Parental-type spleen cells or thoracic duct lymphocytes (TDL), 1 when injected under the renal capsules of genetically tolerant F1 hybrid recipients, initiate an inflammatory reaction that results in the local destruction of tissue in the rat (1). Elkins has described many aspects of this local graft-versus-host (GVH) reaction, repeatedly stressing the requirement for hematogenous cells of the host to sustain an ongoing reaction (2-4). As described, the local GVH reaction appears to be an in vivo counterpart of a one-way mixed lymphocyte reaction in which the host cells serve primarily as the source of the histocompatibility (H) antigens that stimulate the donor cells to enlarge, divide, and destroy target tissues (5, 6). The situation in vivo, however, may well be more complex, particularly with respect to the role of the host cell. Host cell proliferation, for example, can be a conspicuous feature in both systemic (7-10) and local (11, 12) GVH reactions.The present experiments were initiated to gain further information about the activities of the host cells. Attention was also directed to the need for free macrophages in the effector mechanism of the local GVH reaction in view of the requirement for these cells for the full expression of another form of cellmediated immunity, the delayed hypersensitivity reaction (13, 14).The results indicate that a high proportion of activated lymphoid cells within the reaction sites was host derived. Other observations suggest that all manifestations of the local GVH reaction could result from the interaction of parental-type T D L with F1 cells of bone marrow origin. Tissue destruction could be effected in the apparent absence of macrophages. The possible effector activities of host lymphocytes are discussed. Materials and MethodsRats.--Highly inbred Lewis (Lew), Brown Norway (BN), and (Lewis X BN)F1 hybrid (L/BN) rats were obtained from Microbiological Associates Inc., Bethesda, Md

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Section: The E2fect Of Mixing Defined Populations Of Parental and Fi supporting

confidence: 84%

THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES

Volkman

1972

The Journal of Experimental Medicine

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“…The presence of anti host CTL in acute GVHD is a longstanding observation [41]. Recent work has demonstrated that in the spleens of B6àF1 acute GVHD mice, anti host CTL are CD8+, MHC I restricted and kill host cells by both the perforin and Fas/FasL pathway [30,33].…”

Section: Ctl Effector Generationmentioning

confidence: 99%

The Parent-into-F1 Model of Graft-vs-Host Disease as a Model of In Vivo T Cell Function and Immunomodulation

Puliaev¹,

Puliaeva²,

Ryan³

et al. 2005

CMCIEMA

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Since its description roughly 30 years ago, the parent-into-F1 model of graft-vs.-host disease has provided insights into the mechanisms of in vivo T cell activation and the pathogenesis of autoimmune conditions. A new and emerging role for the P-->F1 model is one of identifying agents with immunomodulatory activity and defining in vivo mechanisms that promote cell mediated or antibody mediated immune responses. Because F1 mice are not irradiated prior to donor cell transfer, the P-->F1 model has in the past not been strictly analogous to human hematopoetic stem cell transplantation. However with the advent of newer non-myeloablative conditioning regimens, the model may assume more relevance. In this article, we first provide a review of relevant earlier fundamental observations followed by a summary of recent work from our laboratory in which acute and chronic GVHD in this model have been used not only to study normal T cell responses in vivo but also to define mechanisms important in the pathogenesis of autoimmunity and immunomodulation.

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“…Similarly, under in vitro conditions, spleen cells from F~ hybrid mice undergoing GVH reactions were recently shown (4) to exert a nonspecific cytotoxic effect upon target cells of syngeneic, allogeneic, or xenogeneic genotype to the parental strain. Moreover, the cytotoxic effect was shown to be dependent on the intensity of GVtI reactions and necessitated direct contact between target cells and metabolically active spleen cells; no lysis could be induced with the cell-free supernatant of cultures of these spleen cells (4).…”

Section: (Received For Publication 3 March 1972)mentioning

confidence: 99%

“…The two procedures will be referred to as macro-and nficrocytotoxicity tests. The corrected per cent Ivsis was calculated by the procedure described before (4).…”

Section: Assays For Target Cell Lysis--to Demonstrate the Cytotoxic mentioning

confidence: 99%

CYTOTOXICITY IN GRAFT-VERSUS-HOST REACTION

Singh

Sabbadini

Sehon

1972

The Journal of Experimental Medicine

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Under in vitro conditions spleen cells from nonirradiated F1 hybrids, in which a (graft-vs.-host) (GVH) reaction had been induced with lymphoid cells of parental origin, lysed nonspecifically target cells, i.e., cells syngeneic or allogeneic to the parental genotypes. Furthermore, tumor cells exposed in vitro to spleen cells of F1 hybrid mice undergoing GVH reaction had markedly decreased ability to grow in syngeneic recipients. Experiments involving inhibition of cytotoxicity with alloantisera indicated that this nonspecific effect was due to host cells. By contrast, spleen cells of lethally irradiated F1 hybrids undergoing GVH reaction lysed specifically the target cells of the genotype against which the parental (donor) cells had been sensitized; this finding further supports the contribution of host cells to the nonspecific cytotoxic effects in GVH reaction. From these results it was deduced that the cytotoxic effects during GVH reaction involve at least two processes: (a) sensitization of the donor cells to the antigens of the recipient resulting in the activation of their potential to lyse specifically the recipient's cells, and (b) activation of the host's cells into a state of nonspecific cytotoxicity, as a consequence of the immunologically specific attack of the donor cells.

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Nonspecific Cytotoxicity in Graft-Versus-Host Reactions

Cited by 12 publications

References 0 publications

THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES

THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES

The Parent-into-F1 Model of Graft-vs-Host Disease as a Model of In Vivo T Cell Function and Immunomodulation

CYTOTOXICITY IN GRAFT-VERSUS-HOST REACTION

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