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The Journal of Immunology, Vol 152, Issue 12 5785-5795, Copyright © 1994 by American Association of Immunologists


ARTICLES

Nitric oxide production by splenic macrophages is not responsible for T cell suppression during acute infection with lactate dehydrogenase- elevating virus

RR Rowland, EA Butz and PG Plagemann
Department of Microbiology, Medical School, University of Minnesota, Minneapolis 55455.

Cellular immune responses of mice are transiently suppressed during acute infection with lactate dehydrogenase-elevating virus (LDV). Immunosuppression of mice correlated with a greatly impaired in vitro proliferative response of the majority of the T cells to Con A or anti- CD3 Abs, which could not be reversed by the addition of rIL-2. We have examined whether the T cell suppression is caused by nitric oxide (NO) produced by activated macrophages, which are observed in acutely infected mice. Spleen macrophages from 3-day LDV-infected mice exhibited a 6- to 10-fold increased potential for producing NO, measured as nitrite or nitrite plus nitrate in the culture fluid, but produced significant amounts of NO in vitro only when incubated with IFN-gamma produced by Con A-stimulated T cells in the spleen cell population. Furthermore, we found that the concentrations of NO produced by macrophages in cultures of spleen cells from LDV-infected mice in the presence of IFN-gamma were insufficient to cause a reduction in the proliferative response of T cells in the spleen cell population. An excess of activated macrophages had to be added to achieve T cell suppression. NO inhibition of Con A-induced T cell proliferation exhibited a very sharp dose-response curve. In one experiment little suppression was observed at NO concentrations equivalent to 12 microM nitrite and below, whereas almost complete inhibition was observed at twice the NO concentration. We conclude that NO is not responsible for T cell suppression in LDV-infected mice.


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C. S. Reiss and T. Komatsu
Does Nitric Oxide Play a Critical Role in Viral Infections?
J. Virol., June 1, 1998; 72(6): 4547 - 4551.
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