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PD‐1 modulates regulatory T cells and suppresses T‐cell responses in HCV‐associated lymphoma
Author(s) -
Ni Lei,
Ma Cheng J,
Zhang Ying,
Nandakumar Subhadra,
Zhang Chun L,
Wu Xiao Y,
Borthwick Thomas,
Hamati Agnes,
Chen Xin Y,
Kumaraguru Uday,
Moorman Jonathan P,
Yao Zhi Q
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.121
Subject(s) - il 2 receptor , t cell , hepatitis c virus , cd8 , cytotoxic t cell , immunology , interleukin 21 , biology , t lymphocyte , lymphoma , regulatory t cell , medicine , virology , cancer research , immune system , virus , in vitro , biochemistry
T regulatory (T R ) cells suppress T‐cell responses that are critical in the development of chronic viral infection and associated malignancies. Programmed death‐1 (PD‐1) also has a pivotal role in regulation of T‐cell functions during chronic viral infection. To examine the role of PD‐1 pathway in regulating T R ‐cell functions that inhibit T‐cell responses during virus‐associated malignancy, T R cells were investigated in the setting of hepatitis C virus‐associated lymphoma (HCV‐L), non‐HCV‐associated lymphoma (non‐HCV‐L), HCV infection alone and healthy subjects (HS). Relatively high numbers of CD4 + CD25 + and CD8 + CD25 + T R cells, as well as high levels of PD‐1 expressions on these T R cells were found in the peripheral blood of subjects with HCV‐L compared with those from non‐HCV‐L or HCV alone or HS. T R cells from the HCV‐L subjects were capable of suppressing the autogeneic lymphocyte response, and depletion of T R cells in peripheral blood mononuclear cells from HCV‐L improved T‐cell proliferation. Additionally, the suppressed T‐cell activation and proliferation in HCV‐L was partially restored by blocking the PD‐1 pathway ex vivo , resulting in both a reduction in T R ‐cell number and the ability of T R to suppress the activity of effector T cells. This study suggests that the PD‐1 pathway is involved in regulating T R cells that suppress T‐cell functions in the setting of HCV‐associated B‐cell lymphoma.