Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. V. F1 mice with secondary chronic GVHD contain F1-reactive allohelper but no allosuppressor T cells.

Abstract

We studied the alloreactive properties of donor T cells obtained from F1 mice that had recovered from the allosuppression of acute graft-vs.-host disease (GVHD) and showed mild symptoms of chronic GVHD, i.e., so-called secondary chronic GVHD. To this end, we used (B10 x DBA/2)F1 mice that had been injected with 10(8) B10 spleen cells 100-150 d previously. Such GVHD F1 mice were repopulated by lympho-hematopoietic cells of donor (B10) origin, which exhibited split tolerance towards the host: Whereas F1-specific donor T helper (Th) cells as well as T cells proliferating in the mixed lymphocyte reaction were readily demonstrable, F1-specific T suppressor (Ts) and T killer (Tk) cells were not, or were hardly, detectable; responses against third-party alloantigens were normal. Upon adoptive transfer to nonirradiated secondary recipients, the B10 cells obtained from the repopulated GVH F1 mice induced F1-specific enlargement of the draining popliteal lymph node and enhancement of the IgG formation therein. B10 cells of the same kind were unable, however, to induce lethal GVHD upon transfer to 950 rad-irradiated secondary (B10 x DBA/2)F1 recipients. We conclude that alloactivated donor Ts/Tk cells disappear from the host at a relatively early stage of GVHD, i.e., at the end of acute GVHD , presumably because they are short-lived. By contrast, the longevity of alloactivated donor Th cells causes the symptoms of secondary chronic GVHD.

Clinicopathologic analysis of renal biopsies after haematopoietic stem cell transplantation

“…This could result in an immunostimulatory state and IC glomerulonephritis resembling lupus nephritis. 12,23,24,[26][27][28][29] The IC-mediated pathophysiology of MGN and the temporal association with GVHD strongly suggests dysregulated humoral immunity in the pathogenesis of MGN. 24 The MGN of Patient 7 was preceded by relapse of CML.…”

Renal involvement in bone marrow transplantation

“…A single cell suspension of donor spleen cells of DBA/2 (H‐2 d ) injected intravenously into recipient (C57BL/10xDBA/2)F1(BDF 1 ; H‐2 b/d ) mice can induce severe chronic GVHR with a rapid increase of autoantibodies bypassing the immunosuppression phase of acute GVHR. In this model, alloactivated donor Ts/Tk cells disappear early from the host in spite of longevity of alloactivated donor Th cells 21 . It has been reported that polyclonal IgM‐ to IgG‐class switch occurs in murine chronic GVHR as well as in spontaneous autoimmune animal models, leading to autoimmunity 29,30 .…”

“…20 Chronic GVHR showing an immunostimulatory state is a result of abnormal cooperation between donor T cells and recipient B cells. 21 In this state, autoantibodies including anti-DNA antibody are produced, resulting in immune complex glomerulonephritis, resembling human lupus nephritis. [22][23][24] Cytokines such as IL-4, TGF-β , IL-1, IL-6, TNF and PDGF are considered to be closely related to T-B cell interaction in murine GVHR and to promote deposition of the extracellular matrix, which leads to hyperfiltration.…”

“…In this model, alloactivated donor Ts/Tk cells disappear early from the host in spite of longevity of alloactivated donor Th cells. 21 It has been reported that polyclonal IgM-to IgG-class switch occurs in murine chronic GVHR as well as in spontaneous autoimmune animal models, leading to autoimmunity. 29,30 IgGclass antibody production in BDF 1 mice includes antibodies to autoantigens (DNA, natural thymocytotoxic autoantibody and mouse red blood cells), and to conventional antigens (ovalbumin and TNP-KLH).…”

Completely allogeneic spleen cells induced cytolytic neonatal tolerance to alloantigens, but failed to establish allo‐helper interactions with host T cells

“…This phenomenon occurs when alloreactive CD4 + Th2 cells polyclonally activate B cells bearing MHC alloantigens. 4 Both cytolytic and allo-helper allogeneic responses are responsible for the different manifestations observed in the graft-versus-host disease developed in humans and animals after injection of immunocompetent cells that recognize alloantigens in the host. 5 In these chimeras, the predominance of cytolytic or helper allogeneic responses determines the appearance of atrophic or lupus-like manifestations, respectively.…”