Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10. D2----B10)

Journal Article · Wed Jan 01 00:00:00 EST 1986 · J. Immunol.; (United States)

OSTI ID:5675323

Ildstad, S T; Wren, S M; Bluestone, J A; Barbieri, S A; Stephany, D; Sachs, D H

Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it.

• OSTI ID: 5675323
• Journal Information: J. Immunol.; (United States), Vol. 1
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BONE MARROW
TRANSPLANTS
GRAFT-HOST REACTION
GRAFTS
IMMUNOSUPPRESSION
LETHAL IRRADIATION
LYMPHOCYTES
MICE
RADIATION CHIMERAS
SKIN
THYMUS CELLS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
HEMATOPOIETIC SYSTEM
IRRADIATION
LEUKOCYTES
MAMMALS
MATERIALS
MOSAICISM
ORGANS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals