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

Abstract

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.

Effects of the novel protein kinase C inhibitor AEB071 (Sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or FTY720

“…1) are consistent with its potent inhibition of the local parent‐to‐F1 GvH reaction in the rat. This mechanistic model of allogeneic immune responses is based on donor allogeneic T‐cell interaction with host B‐cells, leading to a swelling of local lymph nodes [29]. Inhibition of early T‐cell activation by AEB [27] can explain the observed reduction in popliteal lymph node swelling.…”

“…Thus, beyond a certain threshold dose level once daily oral dosing of AEB may be sufficient to achieve a therapeutic effect. Conventional immunosuppressive drugs such as cyclosporine have previously been shown to be highly active in rat GvH [24,29]. The marked activity of oral AEB in the rat GvH model (Fig.…”

“…This GvH model was described previously [29]. Briefly, 20 million spleen cells from male donor Wistar/F rats were injected into the right footpads of recipient male (Wistar × Fisher) F1 rats on day 1.…”

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

“…Putative donor-derived allo-antibodies will therefore bind mainly to tissue components of the host and may be difficult to detect in the serum unless circulating donor cells are screened for B cell receptor specificities. We know that the transfusion of PVG T cells into semi-allogeneic F 1 (PVG × DA) hybrid recipients induces auto-antibodies against basal membranes of the skin (Rolstad, 1985). Increased serum levels of antibodies against heat-shock proteins are associated with acute and chronic GvHD (Goral et al, 1995, 2002).…”

Immunosuppressive effects of 2-acetyl-4-tetrahydroxybutyl imidazole (THI) in the rat

“…A host ver.sus graft reaction was induced in the popliteal lymph node by injecting allogeneic (BN x F344)FI spleen cells into a parental strain rat (Ford, Burr & Simonscn, 1970: Rolstad, 1985. Into each hind foot-pad ofanF344 recipient rat, 10^ cells in 01 ml PBS were injected, 8 days after the start of THI treatment.…”