title: Effect of activated human polymorphonuclear leucocytes on T lymphocyte proliferation and viability.
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.
authors.affiliation: Haematology Research Group, Christchurch Hospital, Christchurch, New Zealand. barry.hock@otago.ac.nz
authors.forename: Barry D
authors.initials: BD
authors.lastname: Hock
authors.forename: Karen G
authors.initials: KG
authors.lastname: Taylor
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Cross
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.forename: Mark B
authors.initials: MB
authors.lastname: Hampton
authors.forename: Judith L
authors.initials: JL
authors.lastname: McKenzie
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D008213:Lymphocyte Activation; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*