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

Goovaerts O, Jennes W, Massinga-Loembé M, Ondoa P, Ceulemans A, Vereecken C, Worodria W, Mayanja-Kizza H, Colebunders R, Kestens L, TB-IRIS Study Gro - PLoS ONE (2015)

Bottom Line: 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.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).Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, 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.

No MeSH data available.


Related in: MedlinePlus

Percentage of activated CD8+ cells in early- and late-onset TB-IRIS patients.This box and Tukey whisker plot represents median percentages and IQR of HLA-DR+/CD38+ cells within CD8+/CD45RO+ T cells for early- and late-onset TB-IRIS patients (red) compared to non-IRIS (blue) controls. Median values and IQR for 16 HIV-TB- (yellow) controls are also represented. Full lines above indicate significant differences between paired patients (Wilcoxon signed-rank test). The level of significance was set to P < 0.05 for all tests. Number of patients (and paired non-IRIS controls) prior to ART were; 18 for early-onset TB-IRIS and 8 for late-onset TB-IRIS. Number of patients (and paired non-IRIS controls) during IRIS event or corresponding control time point were; 16 for early-onset TB-IRIS and 9 for late-onset TB-IRIS.
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pone.0133924.g003: Percentage of activated CD8+ cells in early- and late-onset TB-IRIS patients.This box and Tukey whisker plot represents median percentages and IQR of HLA-DR+/CD38+ cells within CD8+/CD45RO+ T cells for early- and late-onset TB-IRIS patients (red) compared to non-IRIS (blue) controls. Median values and IQR for 16 HIV-TB- (yellow) controls are also represented. Full lines above indicate significant differences between paired patients (Wilcoxon signed-rank test). The level of significance was set to P < 0.05 for all tests. Number of patients (and paired non-IRIS controls) prior to ART were; 18 for early-onset TB-IRIS and 8 for late-onset TB-IRIS. Number of patients (and paired non-IRIS controls) during IRIS event or corresponding control time point were; 16 for early-onset TB-IRIS and 9 for late-onset TB-IRIS.

Mentions: To assess the putative role of an overly-activated T cell compartment in TB-IRIS, the percentage of activated (HLA-DR+/CD38+) memory CD8+ T lymphocytes in fresh peripheral whole blood samples was compared between TB-IRIS patients and non-IRIS controls (Fig 3). We observed a lower percentage of activated CD8+ T cells in early-onset TB-IRIS patients prior to ART (77% vs. 82%, p = 0.014) compared to non-IRIS controls, but no differences during IRIS event. Similarly, we observed a lower percentage of activated CD8+ T cells prior to ART in late-onset TB-IRIS patients compared to non-IRIS controls (71% vs. 83%, p = 0.012), but no differences during IRIS event. As expected, both early- and late-onset TB-IRIS patients showed significantly elevated percentages of activated CD8+ T cells compared to HIV-TB- controls at any given time point (p ≤ 0.001).


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

Goovaerts O, Jennes W, Massinga-Loembé M, Ondoa P, Ceulemans A, Vereecken C, Worodria W, Mayanja-Kizza H, Colebunders R, Kestens L, TB-IRIS Study Gro - PLoS ONE (2015)

Percentage of activated CD8+ cells in early- and late-onset TB-IRIS patients.This box and Tukey whisker plot represents median percentages and IQR of HLA-DR+/CD38+ cells within CD8+/CD45RO+ T cells for early- and late-onset TB-IRIS patients (red) compared to non-IRIS (blue) controls. Median values and IQR for 16 HIV-TB- (yellow) controls are also represented. Full lines above indicate significant differences between paired patients (Wilcoxon signed-rank test). The level of significance was set to P < 0.05 for all tests. Number of patients (and paired non-IRIS controls) prior to ART were; 18 for early-onset TB-IRIS and 8 for late-onset TB-IRIS. Number of patients (and paired non-IRIS controls) during IRIS event or corresponding control time point were; 16 for early-onset TB-IRIS and 9 for late-onset TB-IRIS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514632&req=5

pone.0133924.g003: Percentage of activated CD8+ cells in early- and late-onset TB-IRIS patients.This box and Tukey whisker plot represents median percentages and IQR of HLA-DR+/CD38+ cells within CD8+/CD45RO+ T cells for early- and late-onset TB-IRIS patients (red) compared to non-IRIS (blue) controls. Median values and IQR for 16 HIV-TB- (yellow) controls are also represented. Full lines above indicate significant differences between paired patients (Wilcoxon signed-rank test). The level of significance was set to P < 0.05 for all tests. Number of patients (and paired non-IRIS controls) prior to ART were; 18 for early-onset TB-IRIS and 8 for late-onset TB-IRIS. Number of patients (and paired non-IRIS controls) during IRIS event or corresponding control time point were; 16 for early-onset TB-IRIS and 9 for late-onset TB-IRIS.
Mentions: To assess the putative role of an overly-activated T cell compartment in TB-IRIS, the percentage of activated (HLA-DR+/CD38+) memory CD8+ T lymphocytes in fresh peripheral whole blood samples was compared between TB-IRIS patients and non-IRIS controls (Fig 3). We observed a lower percentage of activated CD8+ T cells in early-onset TB-IRIS patients prior to ART (77% vs. 82%, p = 0.014) compared to non-IRIS controls, but no differences during IRIS event. Similarly, we observed a lower percentage of activated CD8+ T cells prior to ART in late-onset TB-IRIS patients compared to non-IRIS controls (71% vs. 83%, p = 0.012), but no differences during IRIS event. As expected, both early- and late-onset TB-IRIS patients showed significantly elevated percentages of activated CD8+ T cells compared to HIV-TB- controls at any given time point (p ≤ 0.001).

Bottom Line: 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.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).Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, 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.

No MeSH data available.


Related in: MedlinePlus