Effect of activated human polymorphonuclear leucocytes on T lymphocyte proliferation and viability

Authors


Correspondence: Dr Barry D. Hock, Haematology Research Group, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. Email: barry.hock@otago.ac.nz

Senior author: Barry D. Hock

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 CD3+ CD28 monoclonal antibodies (mAb) as a readout. We demonstrate that in vitro activated PMN (PMNact) can, without any T-cell interaction, induce apparent T-cell suppression by inhibiting the stimulatory capacity of the CD3 mAb. However, a cell-directed suppression of T-cell proliferation was observed when PMNact 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 PMNact, suppressed T cells could respond normally to further stimulation. In addition to suppressing proliferation, co-culture with PMNact 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.

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