Clonal deletion of V β814-bearing T cells in mice transgenic for mammary tumour virus

Acha‐Orbea, Hans; Shakhov, Alexander N.; Scarpellino, Léonardo; Kolb, E.; Müller, V; Vessaz-Shaw, Annelyse; Fuchs, Regula; Blöchlinger, Karen; Rollini, Pierre; Billotte, Jérôme; Sarafidou, Maria; MacDonald, H. Robson; Diggelmann, Heidi

doi:10.1038/350207a0

Cited by 272 publications

(136 citation statements)

References 48 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…Finally, through the binding to the B-cell-specific Oct-2 factor, but possibly to the ubiquitous Oct-1 as well (49), the octamer sites may play a role in the transcription of MMTV in lymphocytes. These are among the first cells infected by the virus in mice (107), and they express a viral LTR-encoded protein with superantigen functions, leading to selective elimination of specific T-cell clones (1,23,38 …”

Section: Discussionmentioning

confidence: 99%

Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity.

Buetti¹

1994

Mol. Cell. Biol.

View full text Add to dashboard Cite

In the mouse mammary tumor virus promoter, a tandem of octamer motifs, recognized by ubiquitous and tissue-restricted Oct transcription factors, is located upstream of the TATA box and next to a binding site for the transcription factor nuclear factor I (NF-I). Their function was investigated with mutant long terminal repeats under different transfection conditions in mouse Ltk-cells and quantitative Si nuclease mapping of the transcripts. In stable transfectants, which are most representative of the state of proviral DNA with respect to both number of integrated DNA templates and chromatin organization, a long terminal repeat mutant of both octamer sites showed an average 50-fold reduction of the basal transcription level, while the dexamethasonestimulated level was unaffected. DNase I in vitro footprinting assays with L-cell nuclear protein extracts showed that the mutant DNA was unable to bind octamer factors but had a normal footprint in the NF-I site. I conclude that mouse mammary tumor virus employs the tandem octamer motifs of the viral promoter, recognized by the ubiquitous transcription factor Oct-i, for its basal transcriptional activity and the NF-I binding site, as previously shown, for glucocorticoid-stimulated transcription. A deletion mutant with only one octamer site showed a marked base-level reduction at high copy number but little reduction at low copies of integrated plasmids. The observed transcription levels may depend both on the relative ratio of transcription factors to DNA templates and on the relative affinity of binding sites, as determined by oligonucleotide competition footprinting. (14,15,21,48,52,61, 82) and progestins (17,20,41). Analysis by linker-scanning (LS) mutagenesis has defined multiple, distinct sequence elements acting cooperatively to achieve maximal glucocorticoid stimulation of the MMTV promoter (15, 16, 52). Two of them are located in DNA segments shown to bind in vitro the purified glucocorticoid receptor: the strongest, distal element (around position -175) cooperates with a weaker proximal one, which in turn requires a nuclear factor I (NF-I) binding site centered around position -70 (2,12,15,16,19,68,106). In vivo, NF-I binding was observed in conjunction with alterations of the chromatin structure brought about by hormone treatment (3,27, 81).In vitro footprinting studies with nuclear protein extracts of mouse tissues showed a protection against DNase I * Phone: (41 21) (-62 to -37) next to the NF-I binding site that are related to the octamer/NF-III recognition motifs and present as a 10-bp direct repeat (65). A similar configuration of adjacent NF-I and NF-III sites is found in the DNA of adenovirus type 2, in which both sites are required for viral DNA replication (84-86). Octamerrelated sequences occur in transcriptional regulatory elements of several genes, including the promoters of histone H2B (100) and of immunoglobulin light-and heavy-chain genes (30,79) and the enhancers of immunoglobulin heavy chain (6, 37), Ul and U2 small nuclear RNAs (25,51,6...

show abstract

Section: Discussionmentioning

confidence: 99%

Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity.

Buetti¹

1994

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…To study this possibility, a number of LTRs were tested for promoter activity in reporter gene assays. In the particle-producing cell (55). SAG gene expression facilitates MMTV infection of T and B Lymphocytes and subsequently of the mammary gland.…”

Section: Htdv/herv-k a Family Coding For Viral Particlesmentioning

confidence: 99%

The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences.

Löwer

Kurth

1996

Proc. Natl. Acad. Sci. U.S.A.

640

505

View full text Add to dashboard Cite

show abstract

“…That view is based on studies of CD4 ϩ cells in mice exposed to minor lymphocyte-stimulating superantigens (43)(44)(45)(46)(47)(48). Deletion of CD4 ϩ cells in these systems is more extensive than deletion of CD8 ϩ cells, although deletion of the latter has also been observed (43, 49 -51).…”

Section: Figurementioning

confidence: 99%

Treatment of Allograft Recipients with Donor-Specific Transfusion and Anti-CD154 Antibody Leads to Deletion of Alloreactive CD8+ T Cells and Prolonged Graft Survival in a CTLA4-Dependent Manner

Iwakoshi

Mordes

Markees

et al. 2000

The Journal of Immunology

202

191

View full text Add to dashboard Cite

A two-element protocol consisting of one donor-specific transfusion (DST) plus a brief course of anti-CD154 mAb greatly prolongs the survival of murine islet, skin, and cardiac allografts. To study the mechanism of allograft survival, we determined the fate of tracer populations of alloreactive transgenic CD8+ T cells in a normal microenvironment. We observed that DST plus anti-CD154 mAb prolonged allograft survival and deleted alloreactive transgenic CD8+ T cells. Neither component alone did so. Skin allograft survival was also prolonged in normal recipients treated with anti-CD154 mAb plus a depleting anti-CD8 mAb and in C57BL/6-CD8 knockout mice treated with anti-CD154 mAb monotherapy. We conclude that, in the presence of anti-CD154 mAb, DST leads to an allotolerant state, in part by deleting alloreactive CD8+ T cells. Consistent with this conclusion, blockade of CTLA4, which is known to abrogate the effects of DST and anti-CD154 mAb, prevented the deletion of alloreactive transgenic CD8+ T cells. These results document for the first time that peripheral deletion of alloantigen-specific CD8+ T cells is an important mechanism through which allograft survival can be prolonged by costimulatory blockade. We propose a unifying mechanism to explain allograft prolongation by DST and blockade of costimulation.

show abstract

Clonal deletion of V β814-bearing T cells in mice transgenic for mammary tumour virus

Cited by 272 publications

References 48 publications

Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity.

Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity.

The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences.

Treatment of Allograft Recipients with Donor-Specific Transfusion and Anti-CD154 Antibody Leads to Deletion of Alloreactive CD8+ T Cells and Prolonged Graft Survival in a CTLA4-Dependent Manner

Contact Info

Product

Resources

About