Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection.
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.
Dion
Marie-Lise
ML
Laboratoire d'Immunologie, Centre de Recherches du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Hôpital Saint Luc, Montreal, QC, Canada.
Bordi
Rebeka
R
Zeidan
Joumana
J
Asaad
Robert
R
Boulassel
Mohammed-Rachid
MR
Routy
Jean-Pierre
JP
Lederman
Micheal M
MM
Sekaly
Rafick-Pierre
RP
Cheynier
Remi
R
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