Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile
Section snippets
Preparation of human T-cells and activation in vitro
Peripheral blood mononuclear cells were isolated from healthy donors by density gradient centrifugation followed by T cell enrichment using Lymphokwik (One Lambda, Canoga Park CA, USA). Contaminating monocytes were removed by adherence to plastic. Purified T cells were >99% CD2+, <1% HLA-DR+ and <5% CD25+ and were maintained in RPMI-AP5 (RPMI-1640 medium containing 20 mM HEP-ES buffer, pH 7.4, 5% autologous plasma, 1% L-glutamine, 1% penicillin/streptomycin and 0.05% 2-mercaptoethanol). For
Ribavirin enhances Type 1 but suppresses Type 2 cytokine secretion by isolated human T cells stimulated with phorbol ester plus ionomycin
Previous data have shown that ribavirin has antiviral activity in vivo and can suppress a T helper cell-dependent, Ab-mediated response. We speculated that these effects may be related to ribavirin-mediated induction of a distinct Type 1/Type 2 cytokine pattern in activated T cells. Therefore we investigated the influence of ribavirin at 5 μM or 10μM on the cytokine pattern in isolated human T cells from 12 donors following polyclonal activation with 10 ng PMA plus 0.5 μg ionomycin (PMA-ION).
Discussion
The results we report here show that the nucleoside analog ribavirin can selectively modulate Type 1 and Type 2 cytokine expression in stimulated human T cells. The ability of this drug to enhance Type 1 responses and diminish Type 2 responses was a function of the dose of ribavirin, and occurred at concentrations substantially below its antiproliferative concentration and in both helper CD4+ and cytotoxic CD8+ T cells. Ribavirin was able to produce a bias toward a Type 1 cytokine response,
Acknowledgements
We thank Dr G. Benichou for critical evaluation of this manuscript and Dr F. N. Zeytin for helpful discussion, and J. Avalos for collection of blood from normal donors and for excellent technical assistance.
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