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

Jack C. Yu, Marianne Webster, Ira J. Fox

Research output: Contribution to journalArticle

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Abstract

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 (Vβ6) reactive against the minor alloantigen Mlsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thy1.2) were tolerized to AKR antigens (H-2k, Mlsa, Thy1.1) 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 >100 days, these animals were studied for the presence of host Vβ6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were Vβ6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed Vβ6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive Vβ6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice.

Original languageEnglish (US)
Pages (from-to)517-522
Number of pages6
JournalJournal of Surgical Research
Volume48
Issue number6
DOIs
StatePublished - Jun 1990

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Clonal Deletion
Bone Marrow
Bone Marrow Cells
T-Lymphocytes
Flow Cytometry
Spleen
Lymph Nodes
Monoclonal Antibodies
Antigens
Chimerism
Mixed Lymphocyte Culture Test
Skin Transplantation
Isoantigens
Whole-Body Irradiation
T-Cell Antigen Receptor
Transplants
Skin

ASJC Scopus subject areas

  • Surgery

Cite this

Clonal deletion : A mechanism of tolerance in mixed bone marrow chimeras. / Yu, Jack C.; Webster, Marianne; Fox, Ira J.

In: Journal of Surgical Research, Vol. 48, No. 6, 06.1990, p. 517-522.

Research output: Contribution to journalArticle

Yu, Jack C. ; Webster, Marianne ; Fox, Ira J. / Clonal deletion : A mechanism of tolerance in mixed bone marrow chimeras. In: Journal of Surgical Research. 1990 ; Vol. 48, No. 6. pp. 517-522.
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