Faculty Collaboration Database

Mycobacterium bovis BCG-induced granuloma formation depends on gamma interferon and CD40 ligand but does not require CD28. Infect Immun 2001 Apr;69(4):2596-603

Date

03/20/2001

Pubmed ID

11254624

Pubmed Central ID

PMC98196

DOI

10.1128/IAI.69.4.2596-2603.2001

Scopus ID

2-s2.0-0035077708 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

Progressive granuloma formation is a hallmark of chronic mycobacterial infection. Granulomas are localized, protective inflammatory reactions initiated by CD4+ T cells, which contribute to control of bacterial growth and blockade of bacterial dissemination. In order to understand the costimulatory requirements that allow CD4+ T cells to directly or indirectly induce granulomas, we studied granuloma formation after 6 weeks in Mycobacterium bovis BCG-infected CD28- and CD40 ligand (CD40L)-deficient mice and compared it to granuloma formation in infected wild-type inbred mice and infected cytokine-deficient mice. We characterized granulomas morphologically in liver sections, analyzed granuloma infiltrating cells by flow cytometry, and measured cytokine production by cultured granuloma cells. CD28-deficient mice have no defect at the local inflammatory site, inasmuch as they form protective granulomas and control bacterial growth. However, there are fewer activated T cells in the spleen compared to infected wild-type animals, and quantitative differences in the cellular composition of the granuloma are observed by flow cytometry. In CD40L-deficient mice, the granuloma phenotype is very similar to the phenotype in gamma interferon (IFN-gamma)-deficient mice. Both IFN-gamma-deficient and CD40L-deficient mice form granulomas which prevent bacterial dissemination, but control of bacterial growth is significantly impaired. The relative proportion of CD4+ T cells in granulomas from both CD28(-/-) and CD40L(-/-) mice is significantly decreased compared with wild-type animals. Both models demonstrate that the phenotype and activation stage of systemic T cells do not always correlate with the phenotype and activation stage of the localized granulomatous response.

Author List

Hogan LH, Markofski W, Bock A, Barger B, Morrissey JD, Sandor M

Author

Brittany Player DO Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
CD28 Antigens
CD40 Ligand
Granuloma
Immunophenotyping
Interferon-gamma
Liver
Mice
Mice, Inbred C57BL
Mycobacterium bovis
T-Lymphocytes
Tuberculosis