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Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2014
-
Abstract
- Loss of IL-27R on T cells results in increased protection from Mycobacterium tuberculosis. Torrado et al. demonstrate that IL-27R−/− T cells show improved fitness that is associated with decreased expression of cell death molecules, maintenance of IL-2 production, and preferential accumulation in the lung parenchyma and around infected macrophages.<br />CD4+ T cells mediate protection against Mycobacterium tuberculosis (Mtb); however, the phenotype of protective T cells is undefined, thereby confounding vaccination efforts. IL-27 is highly expressed during human tuberculosis (TB), and absence of IL-27R (Il27ra) specifically on T cells results in increased protection. IL-27R deficiency during chronic Mtb infection does not impact antigen-specific CD4+ T cell number but maintains programmed death-1 (PD-1), CD69, and CD127 expression while reducing T-bet and killer cell lectin-like receptor G1 (KLRG1) expression. Furthermore, T-bet haploinsufficiency results in failure to generate KLRG1+, antigen-specific CD4+ T cells, and in improved protection. T cells in Il27ra−/− mice accumulate preferentially in the lung parenchyma within close proximity to Mtb, and antigen-specific CD4+ T cells lacking IL-27R are intrinsically more fit than intact T cells and maintain IL-2 production. Improved fitness of IL-27R–deficient T cells is not associated with increased proliferation but with decreased expression of cell death–associated markers. Therefore, during Mtb infection, IL-27R acts intrinsically on T cells to limit protection and reduce fitness, whereas the IL-27R–deficient environment alters the phenotype and location of T cells. The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB.
- Subjects :
- Adult
Antigens, Differentiation, T-Lymphocyte
CD4-Positive T-Lymphocytes
Male
T cell
Immunology
Programmed Cell Death 1 Receptor
Biology
Research & Experimental Medicine
Article
Interleukin-7 Receptor alpha Subunit
Interleukin 21
Mice
Antigens, CD
medicine
Immunology and Allergy
Cytotoxic T cell
Animals
Humans
Tuberculosis
Lectins, C-Type
IL-2 receptor
Receptors, Cytokine
Receptors, Immunologic
Interleukin 3
Mice, Knockout
Science & Technology
ZAP70
Interleukins
Mycobacterium tuberculosis
Receptors, Interleukin
Natural killer T cell
3. Good health
medicine.anatomical_structure
Medicine, Research & Experimental
Major infection
Interleukin 12
Trans-Activators
Female
Life Sciences & Biomedicine
Subjects
Details
- ISSN :
- 15409538
- Volume :
- 212
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- The Journal of experimental medicine
- Accession number :
- edsair.doi.dedup.....020135a412334a65893a35d0e2537965