title: Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection.
abstract: In chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)-mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery. To circumvent this, we used the sj/betaTREC ratio, a robust index of thymopoiesis that is independent of peripheral T-cell proliferation, to evaluate the thymic contribution to the preservation and restoration of naive CD4+ T cells. We show that the loss of naive and total CD4+ T cells is the result of or is exacerbated by a sustained thymic defect, whereas efficient thymopoiesis supports naive and total CD4+ T-cell maintenance in slow progressor patients. In ART-treated patients, CD4+ T-cell recovery was associated with the normalization of thymopoiesis, whereas the thymic defect persisted in aviremic patients who failed to recover CD4+ T-cell counts. Overall, we demonstrate that efficient thymopoiesis is key in the natural maintenance and in therapy-mediated recovery of naive and total CD4+ T cells.
authors.affiliation: Laboratoire d'Immunologie, Centre de Recherches du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Hôpital Saint Luc, Montreal, QC, Canada.
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Dion
authors.forename: Rebeka
authors.initials: R
authors.lastname: Bordi
authors.forename: Joumana
authors.initials: J
authors.lastname: Zeidan
authors.forename: Robert
authors.initials: R
authors.lastname: Asaad
authors.forename: Mohammed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Micheal M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.forename: Remi
authors.initials: R
authors.lastname: Cheynier
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D038041:Lymphopoiesis / Q000187:drug effects; D008875:Middle Aged; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology