Interleukin-12 administration in retroviral infection of mice increases the potential to produce functional dendritic cells from bone marrow stem cells

Rauscher leukaemia virus (RLV) infection in mice causes production of lymph node and skin dendritic cells (DC) that fail to stimulate a primary mixed leukocyte reaction (MLR). Treatment of mice with IL-12 around the time of i nfection results in DC with normal stimulatory function (N.J. Williams, J.J . Harvey, I. Duncan, R.F.G. Booth, S.C, Knight, Cell Immunol. 183 (1988) 12 1-130). Here we derived DC from mouse bone marrow by culture with granulocy te macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor -alpha (TNF-alpha) for 10-12 days; DC were generated from bone marrow cells taken from normal mice, from mice injected 15 days earlier with RLV or fro m those receiving RLV plus five daily doses of 100 ng of IL-12 starting 2 d ays before infection. Infection of the DC with RLV was assessed from nested PCR with doubling dilutions of DNA and the capacity of DC to stimulate a M LR was tested. DC derived from bone marrow of IL-12 treated animals showed at least twice the level of infection with RLV as those from non-treated an imals although infection never exceeded 20% of the cells. DC derived from b one marrow of mice given RLV caused negligible stimulation of the MLR but t hose from mice additionally treated with IL-12 functioned normally. Thus, t reatment of mice with IL-12 promoted the potential of stem cells taken 12 d ays after the last IL-12 injection to develop into functional DC despite in creased infection with virus. Treatment of mice with IL-12 may have a long term effect on the potential growth of DC from stem cells which may contrib ute to the potency of this cytokine in promoting cell mediated immune respo nses. (C) 1999 Elsevier Science B.V. All rights reserved.