Abstract
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 (PMN
act
) 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 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.