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Effect of activated human polymorphonuclear leucocytes on T lymphocyte proliferation and viability
Author(s) -
Hock Barry D.,
Taylor Karen G.,
Cross Nicholas B.,
Kettle Anthony J.,
Hampton Mark B.,
McKenzie Judith L.
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12004
Subject(s) - viability assay , t cell , cell growth , myeloperoxidase , catalase , microbiology and biotechnology , nitric oxide , chemistry , arginase , biology , in vitro , biochemistry , arginine , immunology , oxidative stress , immune system , endocrinology , inflammation , amino acid
Summary Human polymorphonuclear leucocytes ( PMN ) are thought to be immunosuppressive. The suppressive mechanism(s) used by PMN are, however, not well defined and in this study they were analysed using T ‐cell responses to CD 3 + CD 28 monoclonal antibodies (m A b) as a readout. We demonstrate that in vitro activated PMN ( PMN act ) can, without any T ‐cell interaction, induce apparent T ‐cell suppression by inhibiting the stimulatory capacity of the CD 3 m A b. However, a cell‐directed suppression of T ‐cell proliferation was observed when PMN act were added to pre‐activated T cells that are already committed to polyclonal proliferation. This suppression was partially reversed by catalase addition ( P < 0·01) and largely reversed by addition of exogenous interleukin‐2 ( P < 0·001) but was not significantly reduced by nitric oxide synthase inhibition, myeloperoxidase inhibition or addition of excess arginine. Following removal of PMN act , suppressed T cells could respond normally to further stimulation. In addition to suppressing proliferation, co‐culture with PMN act also induced a significant decrease in T ‐cell viability that was reversed by catalase addition ( P < 0·05). The addition of the arginase inhibitor N ‐hydroxy‐nor‐ l ‐arginine induced both a further significant, catalase‐sensitive, loss in T ‐cell viability and increased nitrite release ( P < 0·001). These data demonstrate that PMN , when activated, can both induce T ‐cell death and reversibly inhibit proliferation of activated T cells. The mechanisms underlying these distinct processes and the effects of arginase inhibitors on PMN induced cytotoxicity merit further investigation.