(P3) Increased exhaustion of gut and blood CD4+ T cells in people living with HIV with insufficient immunologic response to antiretroviral therapy

Författare/Medförfattare

Kristina Berg Lorvik(1)(2)(3), Malin Holm Meyer-Myklestad(2)(4), Asle Medhus(5), Dag Kvale (2)(4), Anne Ma Dyrhol-Riise(2)(4), Dag Henrik Reikvam(2) & Kjetil Tasken(1)(3)(4)

Affiliates

Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Norway(1) Department of Infectious Diseases, Oslo University Hospital, Norway(2) Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Norway(3) Institute of Clinical Medicine, University of Oslo, Norway(4) Department of Gastroenterology, Oslo University Hospital, Norway(5)

Abstract

Background: The prognosis for people living with HIV (PLHIV) has improved greatly over the last decades. Still, some patients do not recover their CD4+ T-cell numbers to sufficient levels in spite of antiretroviral treatment-induced viral suppression. This immunologic non-responder (INR) group of PLHIV has increased risk of death and non-AIDS related morbidity such as cardiovascular disease. We studied whether INR patients display a more exhausted T-cell phenotype compared to immunological responders (IR).
Methods: Blood samples and biopsies from the terminal ileum and sigmoid colon were collected from 19 INR, 20 IR and 20 HIV-negative donors. Peripheral and lamina propria mononuclear cells were analyzed with a 14-color flow cytometry panel to investigate the expression of exhaustion markers PD1, TIGIT, Tim-3, LAG-3, CD160, CD57 and KLRG1, in addition to T cell surface markers including gut homing markers. Immunohistochemistry was applied to detect PD1 ligand (PD-L1)
Results: We found that INRs have more exhausted CD4+ T cells in both blood and gut. In blood INRs have more activated gut homing CD4+ T cells than IRs but these cells did not display more exhaustion markers than activated non-gut homing CD4+ T cells. Interestingly, immunohistochemistry staining of gut biopsies showed that neither INR nor IR expressed PD-L1.
Conclusion: INR have a more exhausted CD4 T-cell pool than IR, both in blood and gut. The lack of PD-L1 upregulation could be one of the factors driving the chronic inflammation seen in HIV patients.