Evidence map›Paper›PMID 22154724›Full record

ArticleHuman immunology2012

Favorable effects of alemtuzumab on allospecific regulatory T-cell generation.

Josh Levitsky, Joseph R Leventhal, Joshua Miller, Xuemei Huang, Li Chen, Dhivya Chandrasekaran, Anat R Tambur, James M Mathew

Abstract read
In one paragraph

Article in Human immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Donor T cells for CAR T cell therapy.Biomarker research · 2022
    Review
  3. Review
  4. Siplizumab selectively depletes effector memory T cells and promotes a relative expansion of alloreactive regulatory T cells in vitro.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Ex vivo-expanded cynomolgus macaque regulatory T cells are resistant to alemtuzumab-mediated cytotoxicity.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2013
    Article
  15. Phase I study of alemtuzumab for therapy of steroid-refractory chronic graft-versus-host disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2013
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Josh LevitskyDivision of Gastroenterology, Hepatology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
Joseph R Leventhal
Joshua Miller
Xuemei Huang
Li Chen
Dhivya Chandrasekaran
Anat R Tambur
James M Mathew
Northwestern University · USJesse Brown VA Medical Center · US

Funding

Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1)UL1TR000150 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LLOYD-JONES, DONALD M · 2012 to 2013
$10.1M
REGULATORY T AND B CELL CIRCUITS IN TRANSPLANTATIONR01DK025243 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MILLER, JOSHUA · 1986 to 2010
$3.9M
NCATS NIH HHS UL1 TR000150NIDDK NIH HHS 2R01DK25243-25A2NIDDK NIH HHS R01 DK025243
6 · The paper itself

Abstract

We studied the effects of alemtuzumab on T-regulatory cells (Tregs) during alloactivation, first by differences in depletion of various naive versus alloactivated cell subsets in peripheral blood of healthy volunteers, then by adding serial concentrations to human leukocyte antigen (HLA)-DR-matched and -mismatched responding and stimulating cells in mixed lymphocyte reaction (MLR). Lymphoproliferation inhibition and the development of proliferating carboxyfluorescein succinimidyl ester (CFSE)-diluted CD4(+)CD25(high)CD127(-)FOXP3(+) (phenotypic) Tregs by flow cytometry were measured. Also, the ability of alemtuzumab-treated versus nontreated MLR generated CD4(+)CD127(-) cells to allospecifically inhibit MLRs and recruit additional responding Tregs was tested. We found a more pronounced refractoriness of alloactivated versus naive CD4(+)CD25(high) cells to alemtuzumab induced lymphodepletion. Alemtuzumab dose dependently inhibited lymphoproliferation while amplifying percentages of MLR-generated Tregs. This was somewhat augmented by human complement addition. CD127(-)CD4(+) cells immunoselected after 7 days from alemtuzumab-treated MLRs allospecifically inhibited lymphoproliferation and recruited additional Tregs in fresh MLR-responding cells, similar to modulators derived from MLRs without drug addition (media). Addition of tacrolimus and sirolimus to alemtuzumab further inhibited MLR proliferation. However, Treg percentages were markedly higher with sirolimus. These results support the notion that alemtuzumab induces immunoregulation in naïve T cells undergoing alloactivation absent presensitization, especially used in conjunction with maintenance SRL.

Indexed as

AlemtuzumabAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCell ProliferationCells, CulturedCell SurvivalDose-Response Relationship, DrugFlow CytometryHumansT-Lymphocytes, RegulatoryAlemtuzumabAntibodies, Monoclonal, HumanizedAntineoplastic Agents

Identifiers

PMID22154724
PMCPMC4064370
OpenAlexW2077534286

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.