CD4 T-cell-mediated heterologous immunity between mycobacteria and poxviruses

UMMS Affiliation

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine; Department of Pathology; Department of Molecular Genetics and Microbiology

Publication Date


Document Type



Animals; Anti-Bacterial Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cross Reactions; Cyclosporine; Female; *Immunity, Innate; Immunologic Factors; Interferon-gamma; Lymphocyte Count; Lymphocytic choriomeningitis virus; Mice; Mice, Inbred C57BL; Mycobacterium bovis; Receptors, Antigen, T-Cell; Splenomegaly; Vaccinia; Vaccinia virus


Life Sciences | Medicine and Health Sciences


The bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis is used in many parts of the world as a vaccine against Mycobacterium tuberculosis. Some epidemiological evidence has suggested that BCG immunization may have unpredicted effects on resistance to other pathogens. We show here in a mouse model that BCG immunization followed by antibiotic treatment to clear the host of the pathogen rendered three strains of mice partially resistant to infection with vaccinia virus (VV) but not to lymphocytic choriomeningitis virus (LCMV). VV-challenged BCG-immune mice developed a striking splenomegaly and elevated CD4 and CD8 T-cell responses by 6 days postinfection (p.i.). However, resistance to VV infection could be seen as early as 1 to 2 days p.i. and was lost after antibody depletion of CD4 T-cell populations. BCG- but not LCMV-immune memory phenotype CD4 T cells preferentially produced gamma interferon (IFN-gamma) in vivo after VV challenge. In contrast, LCMV-immune CD8 T cells preferentially produced IFN-gamma in vivo in response to VV infection. In BCG-immune mice the resistance to VV infection and VV-induced CD4 T-cell IFN-gamma production were ablated by cyclosporine A, which inhibits signaling through the T-cell receptor. This study therefore demonstrates CD4 T-cell-mediated heterologous immunity between a bacterium and virus. Further, it poses the question of whether BCG immunization of humans alters resistance to unrelated pathogens.

DOI of Published Version



J Virol. 2009 Apr;83(8):3528-39. Epub 2009 Feb 4. Link to article on publisher's site

Journal/Book/Conference Title

Journal of virology

Related Resources

Link to Article in PubMed

PubMed ID