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

• Published in: PloS one 2015-07, Vol.10 (7), p.e0133924-e0133924
• Main Authors: Goovaerts, Odin, Jennes, Wim, Massinga-Loembé, Marguerite, Ondoa, Pascale, Ceulemans, Ann, Vereecken, Chris, Worodria, William, Mayanja-Kizza, Harriet, Colebunders, Robert, Kestens, Luc
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Analysis; Antibodies; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Care and treatment; CC chemokine receptors; CCR7 protein; CD27 antigen; CD38 antigen; CD4 antigen; CD4 Lymphocyte Count; CD8 antigen; Cell activation; Cytometry; Development and progression; Female; Flow cytometry; Highly active antiretroviral therapy; Histocompatibility antigen HLA; HIV; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Immune reconstitution; Immune Reconstitution Inflammatory Syndrome - etiology; Immunologic Memory; Inflammation; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Maturation; Middle Aged; Patients; Pretreatment; Prospective Studies; Risk factors; Sexually transmitted diseases; STD; T cell receptors; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tuberculosis; Tuberculosis - complications; Tuberculosis - drug therapy; Viral Load
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133924

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. 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. 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). 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.