Critical stoichiometric ratio of CD4+ CD25+ FoxP3+ regulatory T cells and CD4+ CD25_ responder T cells influence immunosuppression in patients with B-cell acute lymphoblastic leukaemia
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Title |
Critical stoichiometric ratio of CD4+ CD25+ FoxP3+ regulatory T cells and CD4+ CD25_ responder T cells influence immunosuppression in patients with B-cell acute lymphoblastic leukaemia
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Creator |
Bhattacharya, Kaushik
Chandra, Sarmila Mandal, Chitra |
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Subject |
Cancer Biology and Inflammatory Disorder Division
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Description |
Regulatory T (Treg) cells act to suppress activation of the immune system and thereby maintain immunological homeostasis and tolerance to selfantigens. The frequency and suppressing activity of Treg cells in general are high in different malignancies. We wanted to identify the role and regulation of CD4+ CD25+ FoxP3+ Treg cells in B-cell acute lymphoblastic leukaemia (B-ALL). We have included patients at diagnosis (n = 54), patients in clinical remission (n = 32) and normal healthy individuals (n = 35). These diagnosed patients demonstrated a lower number of CD4+ CD25+ cells co-expressing a higher level of FoxP3, interleukin-10, transforming growth factor-b and CD152/CTLA-4 than the normal population. Treg cells from patients showed a higher suppressive capability on CD4+ CD25 responder T (Tresp) cells than normal. The frequency and immunosuppressive potential of CD4+ CD25+ FoxP3+ Treg cells became high with the progression of malignancy in B-ALL. Relative distribution of Tresp and Treg cells was only ~5 : 1 in B-ALL but ~35 : 1 in normal healthy individuals, further confirming the elevated immunosuppression in patients. A co-culture study at these definite ex vivo ratios, indicated that Treg cells from B-ALL patients exhibited higher immunosuppression than Treg cells from normal healthy individuals. After chemotherapy using the MCP841 protocol, the frequency of CD4+ CD25+ cells was gradually enhanced with the reduction of FoxP3, interleukin-10 positivity corresponded with disease presentation, indicating reduced immunosuppression. Taken together, our study indicated that the CD4+ CD25+ FoxP3+ Treg cells played an important role in immunosuppression, resulting in a positive disease-correlation in these patients. To the best of our knowledge, this is the first detailed report on the frequency, regulation and functionality of Treg cells in B-ALL. |
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Publisher |
Blackwell Publishing
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Date |
2014
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/2171/1/IMMUNOLOGY__V__142_(_1)124%2D139;2014[116].pdf
Bhattacharya, Kaushik and Chandra, Sarmila and Mandal, Chitra (2014) Critical stoichiometric ratio of CD4+ CD25+ FoxP3+ regulatory T cells and CD4+ CD25_ responder T cells influence immunosuppression in patients with B-cell acute lymphoblastic leukaemia. Immunology, 142 (1). pp. 124-139. |
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Relation |
http://dx.doi.org/10.1111/imm.12237
http://www.eprints.iicb.res.in/2171/ |
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