Clonal deletion: A mechanism of tolerance in mixed bone marrow chimeras

Journal Article · Fri Jun 01 00:00:00 EDT 1990 · Journal of Surgical Research; (USA)

DOI:https://doi.org/10.1016/0022-4804(90)90223-O· OSTI ID:6644458

Yu, J C; Webster, M; Fox, I J ^[1]

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1. Univ. of Pennsylvania School of Medicine, Philadelphia (USA)

The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice.

• OSTI ID: 6644458
• Journal Information: Journal of Surgical Research; (USA), Vol. 48:6; ISSN 0022-4804
• 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 CELLS
TRANSPLANTS
LYMPHOCYTES
RECEPTORS
SKIN
GRAFTS
CELL FLOW SYSTEMS
CLONE CELLS
IMMUNE REACTIONS
MICE
MONOCLONAL ANTIBODIES
RADIATION CHIMERAS
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CELL CULTURES
CHIMERAS
CONNECTIVE TISSUE CELLS
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MOSAICISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals