AEGiS-11IAC: Comparing cytokine responses in different lymphoid tissues during acute infection of macaques inoculated with a pathogenic SIVmac251.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Comparing cytokine responses in different lymphoid tissues during acute infection of macaques inoculated with a pathogenic SIVmac251.

Int Conf AIDS 1996 Jul 7-12; 11:12 (abstract no. We.A.384)
Cheret A, Le Grand R, Caufour P, Dereuddre-Bosquet N, Matheux F, Neildez O, Maestrali N, Theodoro F, Benveniste O, Vaslin B, Dormont D; CEA/DSV/DRM/SNV, Fontenay aux Roses, France. Fax: (33)-1- 46 54 77 26.

OBJECTIVE: Our aim was to investigate the expression of mRNA monokines (IL-6; TNF-alpha; IL-1beta; IL-10) and IFN-gamma during the acute phase of the infection of cynomolgus macaques inoculated intravenously with a pathogenic isolate of SIVmac251. The quantification of mRNA was performed concomitantly in unmanipulated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs) and mononuclear cells obtained from bronchoalveolar lavages (BALMCs).

METHODS: Four macaques were inoculated intravenously with 4 intravenous-AID50 of a pathogenic isolate of SIVmac251. In order to investigate the effects of a reduced viral load on the expression of the cytokines studied, two monkeys received 30 mg/kg/day of didanosine (ddI) by subcutaneous route. We used semi-quantitative RT-PCR to monitor the expression of cytokine mRNA. The kinetics of hematological, virological and immunological changes were determinated simultaneously.

RESULTS: The two non-treated monkeys became infected and seroconverted, whereas the ddI treated monkeys seemed to be protected (at least until day 35 p.i.). We did not detect any statisticaly significant overexpression of monokine mRNA in PBMCs; however, in LNMCs, where viral replication is elevated and stable, and in the BALMCs (containing nearly 95% of macrophages) overexpression of TNF-alpha, IL-6, IL-10 mRNA was noticed coinciding with the peak of systemic viral replication. IFN-gamma mRNA expression were mostly undetectable in the PBMCs and the LNMCs. On the contrary, a progressive overexpression of IFN-gamma mRNA, starting two weeks after experimental inoculation, was observed only in the BALMCs of the non-treated monkeys. By the same time, we detected a marked increase of the CD8+ lymphocyte percentage in the BAL fluids by FACS analysis.

CONCLUSIONS: Taking together, our results point out the importance of a comparative study of the expression of cytokines in different tissues. This suggests the close interactions between monocytes/macrophages monokine expression and viral replication, as well as the role of IFN-gamma in the setting of lung cellular immunity to SIV infection. Thus, infection of macaques with a pathogenic SIVmac provides a relevant animal model to investigate the cytokine network dysregulation during HIV infection.

Keywords: AEGIS, SIV, Cytokines, Lymphoid Tissue, Macaca, Interleukin-10, CD8-Positive T-Lymphocytes, Interleukin-6, Interleukin-1, Macaca fascicularis, RNA, Messenger, Tumor Necrosis Factor, Lymph Nodes, Didanosine, Viral Load, Macrophages, Animal, ICA11

960707
WeA384