Title
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Lower pre-treatment T cell activation in early- and late-onset tuberculosis-associated immune reconstitution inflammatory syndrome
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Author
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Institution/Organisation
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TB-IRIS Study Grp
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Abstract
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Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p<0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late-but not early- onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. |
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Language
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English
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Source (journal)
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PLoS ONE
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Publication
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2015
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ISSN
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1932-6203
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DOI
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10.1371/JOURNAL.PONE.0133924
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Volume/pages
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10
:7
(2015)
, 15 p.
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Article Reference
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e0133924
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ISI
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000358622000174
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Pubmed ID
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26208109
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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