Mouse Mx protein, an interferon (IFN)-induced nuclear protein, confers selective resistance to influenza virus. We show here that, as with influenza virus-resistant Mx+ mouse embryo cells, influenza virus mRNA accumulation and protein synthesis are strongly inhibited in rat embryo cells treated with IFN-0d$. IFN-x$/ induced in rat cells the synthesis of Mx-related mRNAs migrating on Northern (RNA) gels as two bands of about 3.5 and 2.5 kilobases which directed the synthesis of three electrophoretically distinct proteins called rat Mx proteins 1, 2, and 3. The three rat proteins were antigenically related to the mouse Mx protein but differed in molecular weight and intracellular location. Rat Mx protein 1 was found predominantly in the nucleus and, on the basis of several criteria, resembled the nuclear mouse Mx protein. It was induced by IFN-aI/, in all 28

Background: The ability of chemokines to regulate Th1 and Th2 responses suggests a role in the pathogenesis of atopic disorders such as allergic asthma where Th2 response dominance has been observed. Although the impact of allergic asthma on local chemokine production in the lung has been the subject of investigation, little is know about the influence of disease progression on peripheral chemokine production. We now report use of whole blood culture and flow cytometry to assess the influence of mild allergic asthma on peripheral T‐cell chemokine expression. Methods: Study participants included patients with mild allergic asthma (n = 7) and nonasthmatic controls (n = 7). Following in vitro stimulation of peripheral venous blood with phorbol 12‐myristate acetate (PMA) and ionomycin, flow cytometry was used to estimate the percentage of CD4+ and CD8+ T cells producing a number of chemokines, including macrophage inflammatory proteins MIP‐1α and MIP‐1β, RANTES (regulated on activation, T‐cell expressed and secreted), monocytic chemotactic protein‐1 (MCP)‐1, and interleukin (IL)‐8, or the cytokines interferon (IFN)‐γ and IL‐4. Serum levels of MIP‐1α, MIP‐1β, RANTES, MCP‐1, IL‐8, IFN‐γ and IL‐4 were also assessed by quantitative ELISA. Results: Intracellular expression of MIP‐1β by CD4+ and CD8+ T cells from allergic asthmatics was significantly reduced in comparison to that observed for nonasthmatics (median = 2.29% (1.75–3.50) vs 4.57% (3.38–6.64), P = 0.05; 14.20% (13.18–17.88) vs 44.10% (30.38–48.70), P = 0.01). Similarly, intracellular expression of MIP‐1α by CD8+ T cells from allergic asthmatics was also significantly lower (3.67% (1.17–5.42) vs 17.10% (4.97–20.43), P = 0.05). Conversely, IL‐8 expression by both CD4+ and CD8+ T cells from allergic asthmatics demonstrated significant enhancement (9.93% (7.77–11.28) vs 4.14% (3.61–7.11), P = 0.05; 8.40% (6.97–10.04) vs 4.98% (3.37–6.08), P = 0.05). Examination of intracellular IFN‐γ and IL‐4 revealed no significant difference in the expression of either cytokine by CD4+ T‐cells from allergic asthmatics and nonasthmatics. In contrast, expression of IFN‐γ was significantly reduced in CD8+ T‐cells from allergic asthmatics (24.60% (21.08–32.50) vs 48.40% (41.50–55.28), P = 0.01). Conclusions: The occurrence in mild allergic asthma of peripheral T‐cell chemokine expression suggestive of a diminished Th1 response, coinciding with marginal change in cytokine profiles indicative of a Th2 response bias, confirms the importance of chemokine involvement in the etiology of allergic asthma. The ability to use whole blood culture to estimate chemokine expression in T cell subsets may ultimately provide a practical means to evaluate disease status and to monitor early intervention therapies which target chemokines.

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