CID：改善胸腺功能或是艾滋病治疗新思路

Reduced Thymic Output Is a Major Mechanism of Immune Reconstitution Failure in HIV-Infected Patients After Long-term Antiretroviral Therapy

Taisheng Li, Ning Wu, Yi Dai, Zhifeng Qiu, Yang Han, Jing Xie, Ting Zhu, and Yanling LiBackground. Approximately 20% of human immunodeficiency virus type 1 (HIV-1)--infected adults do not normalize their CD4⁺ T lymphocytes after long-term effective highly active antiretroviral therapy (HAART). The mechanistic basis for this failure is unclear.

Methods. Seventy-four patients were followed up regularly for 3–7 years. Patients with undetectable plasma viral load (<50 copies/mL) for over 12 months were further classified into 2 groups: (1) immunological nonresponders, whose CD4⁺ T-cell count was <200/μL or <20% compared with baseline; and (2) immunological responders, whose CD4⁺ T-cell count was >300/μL or >30% compared with baseline.

Results. Compared with 17 immunological responders, 13 immunological nonresponders had a lower magnitude of naive CD4⁺ T-cell increase, a lower percentage of recent thymic immigrants (CD31⁺%), and a higher percentage of activated CD8⁺ T cells. Furthermore, unlike CD4⁺ T cells, which increased along with the decrease of viral load, the percentage of recent thymic immigrants (CD31⁺%) had little change in the majority of patients. These data were fit into a mathematical model, , from which we deduced that the initial rate of CD4⁺ T-cell restoration is associated significantly with the percentage of recent thymic immigrants (CD31⁺%).

Conclusions. Our data indicate that the failure to restore CD4⁺ T-cell count following HAART was associated primarily with a defect in recent thymic immigrants, which suggests the existence of thymus exhaustion.