Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/69107
Author(s): John E Pearl
Egidio Torrado
Michael Tighe
Jeffrey J Fountain
Alejandra Solache
Tara Strutt
Susan Swain
Rui Appelberg
Andrea M Cooper
Title: Nitric oxide inhibits the accumulation of CD4+CD44hiTbet+CD69lo T cells in mycobacterial infection
Issue Date: 2012
Abstract: 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.
Subject: Medicina básica
Basic medicine
Scientific areas: Ciências médicas e da saúde::Medicina básica
Medical and Health sciences::Basic medicine
URI: https://repositorio-aberto.up.pt/handle/10216/69107
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: https://creativecommons.org/licenses/by-nc/4.0/
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

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