Increased Tryptophan Catabolism is Associated with Increased Frequency of CD161+Tc17/MAIT Cells, and Lower CD4+ T cell Count in HIV-1 infected Patients on cART after Two Years of Follow-up

• Published in: Journal of acquired immune deficiency syndromes (1999)
• Main Authors: Gaardbo, Julie Christine, Trøseid, Marius, Stiksrud, Birgitte, Midttun, Øivind, Ueland, Per Magne, Ullum, Henrik, Nielsen, Susanne Dam
• Format: Journal Article
• Language: English
• Published: United States 11.07.2015
• ISSN: 1944-7884

HIV infection is associated with increased ratio between kynurenine and tryptophan (KTR) in plasma, increased microbial translocation, expansion of Tregs and depletion of Tc17/mucosa associated invariant T cells (MAIT) cells. The association between these parameters and the impact of KTR on CD4+ T cell recovery in HIV-infected patients on cART after two years of follow-up was investigated. Forty-one HIV-infected individuals treated with cART for a minimum of two years were included. Tregs, CD161+Tc17/MAIT cells, naïve cells, immune activation, senescence and apoptosis were measured using flow cytometry. Soluble CD14, LPS and tryptophan metabolites in plasma were measured retrospectively prior to cART and at inclusion initiation using Limulus Amebocyte Lysate colometric assay, ELISA, and tandem mass spectrometry, respectively. KTR was calculated, and patients were divided in two groups defined by high vs. low KTR. The CD4+ T cell count was determined at inclusion and after two years of follow-up. The KTR decreased following cART initiation. Patients on cART with high KTR displayed an immunological profile with high sCD14, high percentage Tregs, low percentage CD161+Tc17/MAIT cells, low percentage naïve cells, low CD4/CD8 ratio and poor immune reconstitution after two years of follow-up compared to patients with low KTR. Our results support the hypothesis that tryptophan catabolism, Indoleamine 2,3-dioxygenase 1 (IDO1) activation, microbial translocation and perturbed distribution of Tregs and CD161+Tc17/MAIT cells are part of a vicious circle that perpetuates exhaustion of the immune system and progression of untreated HIV infection and challenge the immune reconstitution in patients on cART.