| Autor: |
Pearl, John E., Torrado, Egidio, Tighe, Michael, Fountain, Jeffrey J., Solache, Alejandra, Strutt, Tara, Swain, Susan, Appelberg, Rui, Cooper, Andrea M. |
| Zdroj: |
European Journal of Immunology; Dec2012, Vol. 42 Issue 12, p3267-3279, 13p |
| Abstrakt: |
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+ CD44hi CD69hi and CD4+ CD44hi CD69lo populations revealed that CD4+ CD44hi CD69lo cells had higher expression of the integrin itgb1/itga4 ( VLA-4, CD49d/ CD29). Inhibition of Nos2 activity allowed increased accumulation of the CD4+ CD44hi T-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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