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Siplizumab selectiv...
Siplizumab selectively depletes effector memory T cells and promotes a relative expansion of alloreactive regulatory T cells in vitro
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- Podesta, Manuel A. (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA;Univ Milan, Milan, Italy;Ist Ric Farmacol Mario Negri IRCCS, Bergamo, Italy
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- Binder, Christian (författare)
- Uppsala universitet,Klinisk immunologi,ITB Med AB, Stockholm, Sweden
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- Sellberg, Felix (författare)
- Uppsala universitet,Klinisk immunologi,ITB Med AB, Stockholm, Sweden
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- DeWolf, Susan (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA
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- Shonts, Brittany (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA
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- Ho, Siu-Hong (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA
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- Obradovic, Aleksandar (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA
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- Waffarn, Elizabeth (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA
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- Danzl, Nichole (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA
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- Berglund, David, 1984- (författare)
- Uppsala universitet,Klinisk immunologi,ITB Med AB, Stockholm, Sweden
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- Sykes, Megan (författare)
- Columbia Univ, Dept Med, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA;Columbia Univ, Dept Microbiol & Immunol, Med Ctr, New York, NY 10032 USA;Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA
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(creator_code:org_t)
- WILEY, 2020
- 2020
- Engelska.
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Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:1, s. 88-100
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Siplizumab, a humanized anti-CD2 monoclonal antibody, has been used in conditioning regimens for hematopoietic cell transplantation and tolerance induction with combined kidney-bone marrow transplantation. Siplizumab-based tolerance induction regimens deplete T cells globally while enriching regulatory T cells (Tregs) early posttransplantation. Siplizumab inhibits allogeneic mixed-lymphocyte reactions (MLRs) in vitro. We compared the impact of siplizumab on Tregs versus other T cell subsets in HLA-mismatched allogeneic MLRs using PBMCs. Siplizumab predominantly reduced the percentage of CD4(+) and CD8(+) effector memory T cells, which express higher CD2 levels than naive T cells or resting Tregs. Conversely, siplizumab enriched proliferating CD45RA(-) FoxP3(HI) cells in MLRs. FoxP3 expression was stable over time in siplizumab-containing cultures, consistent with enrichment for bona fide Tregs. Consistently, high-throughput TCR beta CDR3 sequencing of sorted unstimulated and proliferating T cells in MLRs revealed selective expansion of donor-reactive Tregs along with depletion of donor-reactive CD4(+) effector/memory T cells in siplizumab-containing MLRs. These results indicate that siplizumab may have immunomodulatory functions that may contribute to its success in tolerance-inducing regimens. Our studies also confirm that naive in addition to effector/memory T cells contribute to the allogeneic MLR and mandate further investigation of the impact of siplizumab on alloreactive naive T cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- immune regulation
- immunosuppressant - fusion proteins and monoclonal antibodies
- T cell specific
- immunosuppression
- immune modulation
- T cell biology
- tolerance
- chimerism
- depletion
- translational research
- science
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Podesta, Manuel ...
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Binder, Christia ...
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Sellberg, Felix
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DeWolf, Susan
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Shonts, Brittany
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Ho, Siu-Hong
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visa fler...
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Obradovic, Aleks ...
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Waffarn, Elizabe ...
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Danzl, Nichole
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Berglund, David, ...
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Sykes, Megan
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