Capacity of genetically different T lymphocytes to induce lethal graft-versus-host disease correlates with their capacity to generate suppression but not with their capacity to generate anti-F1 killer cells. A non-H-2 locus determines the inability to induce lethal graft-versus-host disease.

Abstract

When comparing, in a murine model, the kind of graft-versus-host (GVH) disease (GVHD) induced by the donor strain DBA/2 on the one hand and several H-2-congenic resistant B10 donor strains on the other, we found that strain DBA/2 was a universal nonkilling GVH donor for H-2-incompatible nonirradiated F1 hybrid recipients. In this respect, DBA/2 T cells differed from those of the H-2-identical donor strain B10.D2 as well as those of other b10 donor strains. The inability of strain DBA/2 to kill by GVH reaction was not limited to certain H-2 incompatibilities in the F1 recipients, but was nonspecific. The inability to kill is determined by a dominant locus not linked to H-2. DBA/2 T cells were also incapable of inducing the severe suppression of hematocrit values, bone marrow erythropoiesis, thymic cell proliferation, and splenic IgG production in the F1 recipients that was observed after the injection of T cell from the B10 strains. However, DBA/2 T cells, in contrast with those of the B10 donor strains, were vigorous stimulators of IgG production in H-2-incompatible F1 hybrid recipients. Surprisingly, strain DBA/2 as well as the B10 donor strains had good capacity to generate anti-F1 TK cells. Taken together, these findings raise the possibility that lethal GVHD disease is not caused, or not caused exclusively, by donor killer T cells, but by those donor T cells that directly or indirectly induce a suppression of cell proliferation in certain vital organs of the recipient.

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.

“…Single-cell suspensions of donor SpC, lymph node cells (LNC), and bone marrow cells (BMC) were prepared as described (12).…”

“…with monoclonal anti-Thy-l.2 (clone F7D5; Olac 1976 Ltd.) and C (12). The percentages of live T lymphocytes after treatmentwith anti-Thy-1.2 and C were determined by indirect immunofluorescence by using a rabbit anti-mouse brain serum in combination with fluorescein isothiocyanate-labeled anti-rabbit IgG (F2190; Dakopatts, Copenhagen, Denmark); the percentage ofT cells spared by the anti-Thy-l.2 treatment did not exceed 2%.…”

“…Cells of GVH F1 mice were typed by a complement (C)-dependent cytotoxicity assay, and the results were expressed as a cytotoxic index (12). Histocompatibility typing of erythrocytes was performed by an indirect Coombs' test by applying the two antisera mentioned above and a rabbit anti-mouse IgG serum (cat.…”

A locus on chromosome 2 influences the development of acute graft-versus-host disease in a murine model

“…Previous work reported by Van Elven et al 31 suggested that the ability of donor mice to induce acute GVHD is a recessive trait. If this is indeed the case, we would expect to see a significant proportion of the B10.D2 BX mice able to induce acute GVHD (those homozygous for B10.D2 alleles at the locus (loci) involved) while few if any DBA/2 BX mice would be able to induce acute GVHD (since none could be homozygous for recessive B10.D2 alleles).…”

“…24,31 Because this is the major pathological outcome of acute GVHD, we aimed to identify genetic loci influencing this aspect of GVHD. To observe weight loss patterns during the first 30 days post-transfer, 1.2-1.5 × 10 8 lymphoid cells were isolated from B10.D2, DBA/2 or B6D2F1 mice and injected into B6D2F1 recipients.…”