Acquired Mls-1a-like clonal deletion in Mls-1b mice.
BALB/c mice (H-2d, Mls-1b) from one colony progressively modify their T cell repertoire during aging, by deleting T cells that express products of the V beta 6 and V beta 8.1 genes of the T cell receptor. Clonal deletion occurs only in 50% of mice between 27 and 43 wk of age, affecting thymus, spleen, and lymph node T cells. The phenomenon is progressive and seems to affect nearly all thymuses between 14 and 19 wk of age. CD4+CD8- mature T cells are more affected than CD4-CD8+ cells. In the thymus, deletion occurs at the stage of immature J11d+ cells expressing a high level of V beta 6, while J11d+V beta 6low-expressing cells are not modified. Clonal deletion is thus an early phenomenon that deletes cells of the immature generative compartment in the thymus. This Mls-1a-like clonal deletion is associated neither with the expression of an Mls-1a-like antigen that could be identified in mixed lymphocyte reaction in vitro, nor with the presence of Mtv-7, the endogenous mouse mammary tumor virus (MMTV) proviral loci. Spleen cells, bone marrow cells, and total thymocytes injected into newborn thymuses cannot induce V beta 6+ cell deletion. However, newborn thymuses grafted into old BALB/c mice behave like their recipients, suggesting that a new antigen, present in these old BALB/c mice, is indeed able to induce an Mls-1a-like clonal deletion. As other BALB/c colonies tested do not behave in same way, the hypothesis of a new exogenous deleting factor rather than a genetic transmission is likely. This may suggest that acquired clonal deletion is a more common phenomenon than expected, and may be the spontaneous reaction of the immune system to the introduction of a new retrovirus or other superantigen.
Institut Nationale de la Santé et de la Recherche Médicale (INSERM) U345, Hôpital Necker, Paris, France.
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Papiernik
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Pontoux
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Gisselbrecht
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002872:Chromosome Deletion; D005434:Flow Cytometry; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D016747:Minor Lymphocyte Stimulatory Antigens / Q000235:genetics* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000637:transplantation; D016042:Transplantation, Heterotopic
D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta