Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. I. Alloreactive suppressor cells rather than killer T cells appear to be the decisive effector cells in lethal graft-vs.-host disease.

Abstract

Splenic T cells from B10 donors were injected into irradiated (B10 x DBA/2)F1 mice. Either 5 or 6 d later, activated donor T cells were recovered from the spleens of these primary F1 (1 degree F1) recipients and transferred to groups of nonirradiated syngeneic F1 (2 degrees F1) recipients. Whereas day-5-activated parental T cells induced the characteristic symptoms of acute graft-vs.-host disease (GVHD) and eventually lethal GVHD, day-6-activated B10 T cells failed to induce acute GVHD but induced symptoms of chronic GVHD. Interestingly, the inability of day-6-activated T cells to induce lethal GVHD could not be ascribed to a lack in anti-F1 T killer cells. The combined results of functional studies indicated that day-6 cells were enriched for alloreactive helper T cells, whereas day-5 cells were enriched for alloreactive suppressor cells. Hence, our findings indicate that acute GVHD and lethal GVHD are caused by alloreactive donor T suppressor but not T killer cells, and that symptoms of chronic GVHD are caused by alloreactive donor T helper cells.

CD4+ and CD8+ Regulatory T Cells Generated Ex Vivo with IL-2 and TGF-β Suppress a Stimulatory Graft-versus-Host Disease with a Lupus-Like Syndrome

“…As reported previously, the transfer of parental D2 T cells to DBF 1 mice caused polyclonal B cell activation, anti-dsDNA autoantibodies, and proteinuria (14). These pathologic effects were abolished by priming D2 T cells with B6 alloantigens in the presence of IL-2 and TGF-␤ (Fig.…”

Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms.

“…In contrast, IL3 release is consistently higher with L3T4+ than with Lyt 2+ cells, a fact which correlates well with the appearance ofgut MCs in GVHR elicited in nonirradiated mice (since MC precursors are radiosensitive); MCs, which differentiate from precursors present in the gut wall under the effect of IL3 release (7,40) Finally, the arrival of donor T cells in the host mucosa has effects other than the elicitation of epithelial damage. There was a marked disappearance of IgA plasma cells, already noted in GVHR of mice (1) and man (43), which may be related to the general haematopoietic suppression, since it was closely paralleled by an haematocrit decrease (Table II), also observed in newborn mice with GVHR induced by selected L3T4 cells (Table III). On (6).…”

“…to stimulate certain of the host cells (1)(2)(3) under conditions that are incompletely understood. One of the main target organs of this complex reaction is the gut, and in man diarrhea is among the earliest manifestations of acute GVHR.…”

“…The activated donor T cells are able to destroy or, conversely, Received for publication 29 July 1985 and in revisedform 27 January 1986. 1. Abbreviations used in this paper: GVHR, graft-vs.-host reaction; IE, intraepithelial; IEL, intraepithelial lymphocytes; IFN, interferon; LN, lymph nodes; LP, lamina propria; MAB, monoclonal antibody; MC, mast cells; MLN, mesenteric lymph nodes; PLN, peripheral lymph nodes; PP, Peyer's patches; and TD, thoracic duct.…”

Destruction of the Intestinal Mucosa after Bone Marrow Transplantation and Graft-versus-Host Disease

“…Investigators using the semiallo geneic models emphasize the villous shorten ing with associated crypt hyperplasia, in creased crypt mitoses, and increased num bers of intraepithelial lymphocytes (IEL) [32][33][34][35]. On the other hand, those studying radia tion chimeras emphasize the foci of crypt necrosis, decreased numbers of crypts, de creased crypt mitoses, and greater overall in jury [7,19,[36][37][38][39]. Thus, while the semiallo geneic model might avoid the complications of immune deficiency and toxicity and is helpful in suggesting hypotheses, it can neither be considered adequate nor always appropriate for understanding intestinal GVHD in human bone marrow recipients.…”