The fate of donor T-cell receptor transgenic T cells with known host antigen specificity in a graft-versus-host disease model
| Autor: | B, Dey, Y G, Yang, F, Preffer, A, Shimizu, K, Swenson, D, Dombkowski, M, Sykes |
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| Rok vydání: | 1999 |
| Předmět: |
Mice
Inbred BALB C T-Lymphocytes Receptors Antigen T-Cell Down-Regulation Graft vs Host Disease Apoptosis Bone Marrow Cells Mice Transgenic CD8-Positive T-Lymphocytes Lymphocyte Activation Clone Cells Mice Inbred C57BL Disease Models Animal Epitopes Mice Acute Disease Animals Female Spleen Whole-Body Irradiation |
| Zdroj: | Transplantation. 68(1) |
| ISSN: | 0041-1337 |
| Popis: | The expansion of transgenic donor CD8+ T-cells with known allospecificity against a host MHC class I alloantigen was examined in a murine graft-versus-host disease (GVHD) model.Lethally irradiated, Ld+ BALB/c mice received bone marrow cells and spleen cells from anti-Ld 2C T-cell receptor (TCR)-transgenic B6 mice, alone or with normal B6 spleen cells. Transgenic TCR-bearing T-cell expansion, apoptosis, and function were monitored at various time points and were correlated with clinical outcome.Fifteen-fold clonal expansion of 2C CD8 cells occurred by day 4 after bone marrow transplantation. Between days 4 and 7, increasing proportions of 2C CD8 cells underwent apoptotic cell death, coincident with a 7-15-fold decline in their numbers. CD8 and TCR expression were down-regulated on 2C CD8 cells by day +4 after bone marrow transplantation, and they were anergic to TCR-mediated stimulation. Clinically, the BALB/c recipients of 2C spleen cells exhibited only minimal chronic GVHD. In contrast, lethally irradiated BALB/c mice receiving similar numbers of non-transgenic B6 bone marrow cells and spleen cells exhibited severe GVHD (median survival time: 28 days). The addition of a small number of 2C spleen cells to the inoculum accelerated GVHD mortality, and 2C CD8 cells showed a similar time course of expansion and decline to that observed in recipients of larger numbers of 2C cells alone.Initial clonal expansion, down-regulation of CD8 and TCR, anergy, and later deletion of graft-versus-host-reactive CD8 cells via apoptosis occurs in lethally irradiated recipients. Expansion of a single CD8 clone produces much less severe GVHD than that induced by a polyclonal, mixed CD4 plus CD8 response. These results have implications for GVHD pathogenesis and its sometimes self-limited nature. |
| Databáze: | OpenAIRE |
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