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Infection and Immunity, November 2002, p. 5997-6004, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.5997-6004.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Nitric Oxide Limits the Expansion of Antigen-Specific T Cells in Mice Infected with the Microfilariae of Brugia pahangi

Richard A. O'Connor and Eileen Devaney^*

Department of Veterinary Parasitology, University of Glasgow, Glasgow G61 1QH, Scotland

Received 9 May 2002/ Returned for modification 29 June 2002/ Accepted 27 July 2002

Infection of BALB/c mice with the microfilariae (Mf) of the filarial nematode Brugia pahangi results in an antigen-specific proliferative defect that is induced by high levels of NO. Using carboxyfluorescein diacetate succinimydl ester and cell surface labeling, it was possible to identify a population of antigen-specific T cells from Mf-infected BALB/c mice that expressed particularly high levels of CD4 (CD4^hi). These cells proliferated in culture only when inducible NO synthase was inhibited and accounted for almost all of the antigen-specific proliferative response under those conditions. CD4^hi cells also expressed high levels of CD44, consistent with their status as activated T cells. A similar population of CD4^hi cells was observed in cultures from Mf-infected gamma interferon receptor knockout (IFN-R^-/-) mice. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining revealed that the CD4⁺ T cells from Mf-infected wild-type mice were preferentially susceptible to apoptosis compared to CD4⁺ T cells from IFN-R^-/- mice. These studies suggest that the expansion of antigen-specific T cells in Mf-infected mice is limited by NO.

Editor: W. A. Petri, Jr.

Present address: The Trudeau Institute, 100 Algonquin Ave., Saranac Lake, NY 12983.

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