Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice

• Published in: Infection and Immunity Vol. 75; no. 3; pp. 1154 - 1166
• Main Authors: Hogan, Laura H, Co, Dominic O, Karman, Jozsef, Heninger, Erika, Suresh, M, Sandor, Matyas
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.03.2007
• Subjects: Animals; Bacterial diseases; Biological and medical sciences; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Movement - genetics; Cell Movement - immunology; Fundamental and applied biological sciences. Psychology; Granuloma - genetics; Granuloma - immunology; Granuloma - prevention & control; Granuloma - virology; Host Response and Inflammation; Human bacterial diseases; Immunologic Deficiency Syndromes - immunology; Immunologic Deficiency Syndromes - pathology; Immunologic Deficiency Syndromes - virology; Infectious diseases; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytic choriomeningitis virus; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microbiology; Mycobacterium bovis; Mycobacterium bovis - immunology; Tuberculosis and atypical mycobacterial infections; Microbiology; Mycobacterium bovis; Rodentia; BCG; Mycobacterial infection; Immunity; Infection; Vertebrata; Mammalia; Tuberculosis; Mouse; Mycobacteriales; T-Lymphocyte; Bacteriosis; Mycobacteriaceae; Bacteria; Actinomycetes
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00943-06

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-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. 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.