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Functionally suppressive CD8 T regulatory cells are increased in patients with multiple myeloma: a cause for immune impairment

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MUTHU RAJA Karthick Raja KUBICZKOVÁ Lenka ŘÍHOVÁ Lucie PISKACEK Martin VŠIANSKÁ Pavla HÉŽOVÁ Renata POUR Luděk HÁJEK Roman

Rok publikování 2012
Druh Článek v odborném periodiku
Časopis / Zdroj Public Library of Science one
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
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Doi http://dx.doi.org/10.1371/journal.pone.0049446
Obor Onkologie a hematologie
Klíčová slova Multiple myeloma; CD4 regulatory T cells; suppressive Treg cells
Přiložené soubory
Popis 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.
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