Nitric oxide inhibits the accumulation of CD4+CD44hiTbet+CD69lo T cells in mycobacterial infection

• Type: Article in International Scientific Journal
• Date: 2012

Authors

John E Pearl (Author) Other; Egidio Torrado (Author) Other; Michael Tighe (Author) Other; Jeffrey J Fountain (Author) Other; Alejandra Solache (Author) Other; Tara Strutt (Author) Other; Susan Swain (Author) Other; Rui Appelberg (Author) ICBAS; Andrea M Cooper (Author) Other

Journal

Title: European Journal of Immunology

Vol. 42

Pages: 3267-3279

ISSN: 0014-2980

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 14 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-2QF

DOI: 10.1002/eji.201142158

Abstract (EN): Animals lacking the inducible nitric oxide synthase gene (nos2-/-) are less susceptible to Mycobacterium avium strain 25291 and lack nitric oxide-mediated immunomodulation of CD4+ T cells. Here we show that the absence of nos2 results in increased accumulation of neutrophils and both CD4+ and CD8+ T cells within the M. avium containing granuloma. Examination of the T-cell phenotype in M. avium infected mice demonstrated that CD4+CD44hi effector T cells expressing the Th1 transcriptional regulator T-bet (T-bet+) were specifically reduced by the presence of nitric oxide. Importantly, the T-bet+ effector population could be separated into CD69hi and CD69lo populations, with the CD69lo population only able to accumulate during chronic infection within infected nos2-/- mice. Transcriptomic comparison between CD4+CD44hiCD69hi and CD4+CD44hiCD69lo populations revealed that CD4+CD44hiCD69lo cells had higher expression of the integrin itgb1/itga4 (VLA-4, CD49d/CD29). Inhibition of Nos2 activity allowed increased accumulation of the CD4+CD44hiT-bet+CD69lo population in WT mice as well as increased expression of VLA-4. These data support the hypothesis that effector T cells in mycobacterial granulomata are not a uniform effector population but exist in distinct subsets with differential susceptibility to the regulatory effects of nitric oxide.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13