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PLoS One. 2015 Jul 24;10(7):e0133924. doi: 10.1371/journal.pone.0133924. eCollection 2015.

Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

Author information

1
Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
2
Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
3
Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, Lambarene, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
4
Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands.
5
Department of Medicine, Mulago Hospital, Kampala, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Infectious Diseases Network for Treatment and Research in Africa (INTERACT), Kampala, Uganda.
6
Department of Medicine, Mulago Hospital, Kampala, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
7
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium.

Abstract

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.

PMID:
26208109
PMCID:
PMC4514632
DOI:
10.1371/journal.pone.0133924
[Indexed for MEDLINE]
Free PMC Article

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