TY - JOUR
T1 - Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection
AU - Dion, Marie Lise
AU - Bordi, Rebeka
AU - Zeidan, Joumana
AU - Asaad, Robert
AU - Boulassel, Mohammed Rachid
AU - Routy, Jean Pierre
AU - Lederman, Micheal M.
AU - Sekaly, Rafick Pierre
AU - Cheynier, Remi
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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/βTREC 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 therapymediated recovery of naive and total CD4 + T cells.
AB - 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/βTREC 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 therapymediated recovery of naive and total CD4 + T cells.
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U2 - 10.1182/blood-2006-09-047308
DO - 10.1182/blood-2006-09-047308
M3 - Article
C2 - 17164338
AN - SCOPUS:33947606768
SN - 0006-4971
VL - 109
SP - 2912
EP - 2920
JO - Blood
JF - Blood
IS - 7
ER -