The Stimulus to Host Cell Proliferation in Graft‐versus‐Host Reactions

Ford, W. L.; Rolstad, Bent; Fossum, Sigbjørn; Hunt, S. V.; Smith, Marilyn E.; Sparshott, Sheila M.

doi:10.1111/j.1365-3083.1981.tb00613.x

Cited by 13 publications

(8 citation statements)

References 35 publications

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“…This is somewhat surprising as in early GVH reactions a significant component of the proliferation is host cell (Ford et al, 1981), presumably mediated by soluble factors in vivo (English, 1982). With regard to the inability to recover FDCP after in vivo injection, the recirculation and co-culture experiments suggest that one major problem is nonspecific cell toxicity generated by normal cells e.g.…”

Section: Discussionmentioning

confidence: 99%

“…We have tried to answer these questions by firstly seeking the activity in situations induced in vivo which parallel those in vitro where IL-3 is produced: namely during the pan-lymphocyte stimulation associated with acute graft versus host disease (GVHD)-a parallel of mitogen stimulation (Ford et al, 1981); and in mice rendered acutely leukaemic after transfusion with WEHI-3b cells. Secondly, we have followed the fate of FDCP cells after injection into normal and irradiated mice.…”

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confidence: 99%

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Studies on the in vivo production of a lymphokine activity, interleukin 3 (IL-3) elaborated by lymphocytes and a myeloid leukaemic line in vitro and the fate of IL-3 dependent cell lines

Garland¹,

Aldridge²,

Wagstaffe³

et al. 1983

Br J Cancer

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Summary Interleukin 3 (IL-3) is produced constituitively by WEHI-3b leukaemic cells and stimulated lymphoid cell populations in vitro. We have investigated the in vivo production of IL-3 in mice rendered leukaemic with WEHI-3b cells and mice stimulated by acute graft versus host disease (GVHD). In leukaemic mice, IL-3 was not found in serum or sonicates of 18-day spleens or bone marrow, although cells from the leukaemic organs were fully competent to elaborate IL-3 in vitro. Further, elaboration of IL-3 by WEHI cells in vitro was not affected by co-culture with normal haemopoietic cells. However, intracellular IL-3 was detected in leukaemic nodules isolated from the liver. Inhibitors specific for IL-3 were not found, although liver-cell conditioned medium and leukaemic nodule sonicates contained potent non-specific inhibitors of cell growth. At 21 days, intracellular IL-3 was also present in spleens and correlated with the presence of nonspecific inhibitors. In GVHD, no evidence for IL-3 elaboration in vivo was found, nor did lymphoid populations affected by GVHD spontaneously elaborate it in vitro; however, their competence to produce it was unaffected, as IL-3 was elaborated on subsequent mitogen stimulation in vitro.We also investigated the recovery and circulation of in vitro ...Indium-labelled IL-3 dependent cells after injection in vivo and the half-life of semi-purified IL-3. Dependent cells were not recovered after injection into irradiated recipients, although the cells recirculated for at least 24 hours. Inability to recover dependent cells was explicable on general cytotoxicity which masked potential recovery. The serum half-life of injected partially purified material with IL-3 activity was short (<30min). We conclude that the elaboration of IL-3 by leukaemic WEHI-3b is not an in vitro artifact and these results are discussed in relationship to other growth factors and the leukaemic state, and the origin of IL-3 dependent lines.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Studies on the in vivo production of a lymphokine activity, interleukin 3 (IL-3) elaborated by lymphocytes and a myeloid leukaemic line in vitro and the fate of IL-3 dependent cell lines

Garland¹,

Aldridge²,

Wagstaffe³

et al. 1983

Br J Cancer

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“…1). Second, when the early proliferative response in the popliteal lymph nodes, say, of strain AA rats receiving strain BB lymphocytes in the foot pad was compared with strain A x C recipients of strain B x C cells, the response was, if anything, more vigorous where the donor and host did not share any MHC haplotypes (Ford et al 1981). Third, when the survival of the allogeneic lymphocytes in the nude recipients was monitored in rat strain combinations where the host was resistant to the GvH reaction (e.g.…”

Section: Gvh Reactions In Athymic Nude Ratsmentioning

confidence: 99%

The Popliteal Lymph Node Graft‐versus‐Host (GvH) Reaction in the Rat: A Useful Model for Studying Cell Interactions in the Immune Response

Rolstad

Blixen

1985

Immunological Reviews

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Simonsen (1962), in his comprehensive review article on GvH reactions, rightly emphasized the great applicability this reaction had in immunological research. A broader implication of GvH reactions than was perhaps expected was evident when the complex interactions between the donor cells the host's immune system were detected. In this review article, one aspect of the donor-host cell interactions is discussed. Using the popliteal lymph node GvH reaction as a model, it has been shown that the hyperplastic response in the lymph node is due to an accumulation and proliferation of cells almost exclusively of host origin. B cells are preferentially activated, and although mitogenic factors are released into the circulation during systemic GvH reactions, the interaction between donor TH cells and host B cells is probably of a more specific nature, involving only those B cells expressing MHC antigens to which the donor cells are able to react. This will presumably lead to a panclonal activation of host B cells with antibody production against a wide variety of antigens. Athymic nude rats are often surprisingly resistant to GvH reactions induced by allogeneic T cells, and this resistance can now be satisfactorily explained in terms of natural resistance mechanisms. Sometimes F1 hybrid rats are also resistant to GvH reactions induced by parental cells, indicating that this resistance may be restricted by non-codominantly inherited genes.

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“…The function of this group of host cells in the GvH reaction is unknown. The subpopulation susceptible to PVG anti-DA serum probably included cells with anti-idiotypic aetivity against some of the injected PVG lymphocytes (McCullagh, 1977), although these are unlikely to have constituted more than a small percentage of the subpopulation (Ford et al, 1981).…”

Section: Partition Of the Gvh Reactivity Of Populations Of (Pvgxfi) Bmentioning

confidence: 99%

The Relationship of the Antigenic Determinants Expressed by Rat Lymphoid Cells to Their Participation in Graft‐versus‐host Reactions

McCullagh¹

1985

Aust J Exp Biol Med

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Summary.The relationship between the graft-versus-host reactivity of lymphocytes from F2 hybrid and backcross rats and their susceptibility to inter-parental strain alloantisera has been investigated. Apart from associations between the immunological responsiveness of individual rats and the extent of alloantiserum susceptibility of their lymphocytes, selective reactivity of groups of lymphocytes that were separable from the general population by means of their alloantiserum susceptibility was observed. Those host lymphocytes which expressed a preponderance of DA-derived determinants were preferentially implicated in graft-versushost reactions elicited by PVG lymphocytes in (PVGxDA)F2 hybrid rats. The anti-(PVGxDA)F| hybrid reactivity of some (PVGxFj) backcross rats was selectively concentrated in that fraction of the lymphocyte population which expressed the highest levels of PVGderived determinants. It is proposed that heterogeneously expressed MHS determinants may have a role in regulating selective participation by subpopulations of lymphocytes in allogeneie reactions.

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The Stimulus to Host Cell Proliferation in Graft‐versus‐Host Reactions

Cited by 13 publications

References 35 publications

Studies on the in vivo production of a lymphokine activity, interleukin 3 (IL-3) elaborated by lymphocytes and a myeloid leukaemic line in vitro and the fate of IL-3 dependent cell lines

Studies on the in vivo production of a lymphokine activity, interleukin 3 (IL-3) elaborated by lymphocytes and a myeloid leukaemic line in vitro and the fate of IL-3 dependent cell lines

The Popliteal Lymph Node Graft‐versus‐Host (GvH) Reaction in the Rat: A Useful Model for Studying Cell Interactions in the Immune Response

The Relationship of the Antigenic Determinants Expressed by Rat Lymphoid Cells to Their Participation in Graft‐versus‐host Reactions

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