MUTHU RAJA, Karthick Raja, Lenka KUBICZKOVÁ, Lucie ŘÍHOVÁ, Martin PISKACEK, Pavla VŠIANSKÁ, Renata HÉŽOVÁ, Luděk POUR and Roman HÁJEK. Functionally suppressive CD8 T regulatory cells are increased in patients with multiple myeloma: a cause for immune impairment. Public Library of Science one, San Francisco, CA, USA: Public Library of Science, 2012, vol. 7, No 11, p. 1-10. ISSN 1932-6203. doi:10.1371/journal.pone.0049446.
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Original name Functionally suppressive CD8 T regulatory cells are increased in patients with multiple myeloma: a cause for immune impairment
Authors MUTHU RAJA, Karthick Raja (356 India, belonging to the institution), Lenka KUBICZKOVÁ (203 Czechia, belonging to the institution), Lucie ŘÍHOVÁ (203 Czechia, belonging to the institution), Martin PISKACEK (40 Austria, belonging to the institution), Pavla VŠIANSKÁ (203 Czechia, belonging to the institution), Renata HÉŽOVÁ (203 Czechia, belonging to the institution), Luděk POUR (203 Czechia) and Roman HÁJEK (203 Czechia, guarantor, belonging to the institution).
Edition Public Library of Science one, San Francisco, CA, USA, Public Library of Science, 2012, 1932-6203.
Other information
Original language English
Type of outcome article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW Full Text
Impact factor Impact factor: 3.730
RIV identification code RIV/00216224:14110/12:00057824
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1371/journal.pone.0049446
UT WoS 000311234600041
Keywords in English Multiple myeloma; CD4 regulatory T cells; suppressive Treg cells
Tags rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 17. 12. 2019 15:32.
Abstract
Multiple myeloma (MM) is a plasma cell malignancy frequently associated with impaired immune cell numbers and functions. In MM, several studies have previously shown that CD4 regulatory T (Treg) cells hamper effector T cell functions and enhance immune dysfunction. In this study, we aimed to prove the presence of functionally suppressive Treg cells expressing CD8 phenotype (CD8 Treg cells) in MM. To the best of our knowledge, this has not been reported previously in MM. METHODS: We analyzed CD8 Treg cells and their transcription factor FoxP3 from 64 newly diagnosed MM patients using flow cytometry and real time-polymerase chain reaction (RT-PCR). RNA profile of cytokines in CD8 Treg cells was also assessed using RT-PCR. CD8 Treg cells from 5 MM patients and 5 healthy donors were functionally evaluated using proliferation assays. RESULTS: CD8 Treg cells (CD8+CD25hi+) were significantly elevated in MM patients (P<0.0001), and their transcription factor FoxP3 expression was also higher in MM (P<0.0001) compared to healthy donors which was evidenced by flow cytometry and RT-PCR analyses. CD8 Treg cells negatively correlated with total lymphocyte count (P = 0.016). Functional studies revealed that CD8 Treg cells isolated from MM patients and healthy donors inhibited proliferation of CD4 T cells in a concentration dependent manner. In the presence of CD8 Treg cells in proliferation assays, level of IFN-gamma was decreased but not IL-10. CD4 T cells from MM patients secreted abnormal level of IL-10 compared to healthy donors (P = 0.01) in proliferation assays without CD8 Treg cells. RNA profile of cytokines from CD8 Treg cells did not differ significantly between MM patients and healthy donors. CONCLUSIONS: These findings show the presence of increased number of functionally suppressive CD8 Treg cells in MM patients. We believe that these suppressive CD8 Treg cells might enhance immune impairment and disease progression in MM.
Links
GAP304/10/1395, research and development projectName: Analýza klonálních progenitorů plazmatických buněk u monoklonálních gamapatií
Investor: Czech Science Foundation, Standard Projects
MSM0021622434, plan (intention)Name: Od klasických prognostických markerů ke klinicky aplikovatelným farmakogenomickým a farmakoproteomickým projektům u mnohočetného myelomu a monoklonálních gamapatií
Investor: Ministry of Education, Youth and Sports of the CR, Research Intents
NT11154, research and development projectName: Úloha mitotické disrupce v B lymfocytech u mnohočetném myelomu
Investor: Ministry of Health of the CR
NT13190, research and development projectName: Molekulární charakteristika centrozomálních abnormalit a jejich prognostický význam pro pacienty s mnohočetným myelomem
Investor: Ministry of Health of the CR
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Muthu_Raja_2012_-_PLOS_One_-Functionally.pdf   File version Potáčová, A. 19. 11. 2012

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  • a concrete person Mgr. Karthick Raja Muthu Raja, Ph.D., učo 106209
  • a concrete person Mgr. Renata Héžová, Ph.D., učo 115438
  • a concrete person Dipl. Ing. Martin Piskáček, Dr. rer. nat., učo 116130
  • a concrete person Mgr. Lenka Bešše, Ph.D., učo 179944
  • a concrete person Mgr. Lucie Říhová, Ph.D., učo 20214
  • a concrete person doc. MUDr. Luděk Pour, Ph.D., učo 20594
  • a concrete person Mgr. Pavla Všianská, Ph.D., učo 211057
  • a concrete person prof. MUDr. Roman Hájek, CSc., učo 33302
  • a concrete person Mgr. Marie Šípková, DiS., učo 437722
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