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Infection and Immunity, March 2007, p. 1154-1166, Vol. 75, No. 3
0019-9567/07/$08.00+0 doi:10.1128/IAI.00943-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Jozsef Karman,1,
Erika Heninger,1
M. Suresh,2 and
Matyas Sandor1*
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706,1 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 537062
Received 13 June 2006/ Returned for modification 9 August 2006/ Accepted 10 December 2006
The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-
)-producing LCMV-specific T cells in liver granulomas and increased local IFN-
. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.
Published ahead of print on 18 December 2006.
Present address: Children's Hospital of Wisconsin, Milwaukee, WI.
Present address: Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, HIM 785, Boston, MA 02115-5817.
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