Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: Clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls-1a controlled by hemopoietic cells in the thymus

Journal Article · Thu Nov 01 04:00:00 EST 1990 · Journal of Experimental Medicine; (USA)

DOI:https://doi.org/10.1084/jem.172.5.1305· OSTI ID:6320327

Speiser, D E; Chvatchko, Y; Zinkernagel, R M; MacDonald, H R ^[1]

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1. Ludwig Institute for Cancer Research, Epalinges (Switzerland)

Elimination of potentially self-reactive T lymphocytes during their maturation in the thymus has been shown to be a major mechanism in accomplishing self-tolerance. Previous reports demonstrated that clonal deletion of self-Mls-1a-specific V beta 6+ T lymphocyte is controlled by a radiosensitive I-E+ thymic component. Irradiation chimeras reconstituted with I-E- bone marrow showed substantial numbers of mature V beta 6+ T cells despite host Mls-1a expression. Analysis of the functional properties of such chimeric T cells revealed a surprising variability in their in vitro reactivity to host Mls-1a, depending on the H-2 haplotype of stem cells used for reconstitution. In chimeras reconstituted with B10.S (H-2s) stem cells, mature V beta 6+ lymphocytes were present but functionally anergic to host-type Mls-1a in vitro. In contrast, in chimeras reconstituted with B10.G (H-2q) bone marrow, nondeleted V beta 6+ cells were highly responsive to Mls-1a in vitro. These findings suggest that clonal anergy of V beta 6+ cells to self-Mls-1a may be controlled by the affinity/avidity of T cell receptor interactions with bone marrow-derived cells in the thymus depending on the major histocompatibility complex class II molecules involved. Furthermore, chimeras bearing host (Mls-1a)-reactive V beta 6+ cells did not differ clinically from those with anergic or deleted V beta 6+ cells and survived more than one year without signs of autoimmune disease. Interestingly, their spleen cells had no Mls-1a stimulatory capacity in vitro. Therefore, regulation at the level of antigen presentation may be an alternative mechanism for maintenance of tolerance to certain self-antigens such as Mls-1a.

• OSTI ID: 6320327
• Journal Information: Journal of Experimental Medicine; (USA), Journal Name: Journal of Experimental Medicine; (USA) Vol. 172:5; ISSN 0022-1007; ISSN JEMEA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW CELLS
CHIMERAS
CONNECTIVE TISSUE CELLS
FUNCTIONS
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MOSAICISM
ORGANS
RADIATION CHIMERAS
RODENTS
SOMATIC CELLS
STEM CELLS
THYMUS
TRANSPLANTS
VERTEBRATES