Association between Larger Thymic Size and Higher Thymic Output in Human Immunodeficiency Virus-Infected Patients Receiving Highly Active Antiretroviral Therapy

To examine the impact of thymic size on immune recovery in patients with human immunodeficiency virus (HIV) infection, the thymus was visualized, using computed tomographic scans, in 25 HIV-infected patients who had received highly active antiretroviral therapy (HAART) for 6‐ 18 months and had levels of viremia ,500 copies/mL. For comparison, 10 control subjects were included in the study. Total and naive CD4 + cell counts were determined by flow cytometry. To determine thymic output, the number of CD4 + cells containing T cell receptor excision circles (TRECs) was measured. Qualitative immune recovery was evaluated by determination of CD4 + T cell receptor repertoire in 19 of the HIV-infected patients. Larger thymic size was associated with higher CD4 + cell counts (r ¼ 0.498; P ¼ .011) and higher CD4 + TREC frequency (r ¼ 0.652; P , .001). Furthermore, patients with abundant thymic tissue seemed to have broader immunologic repertoires, compared with patients with minimal thymic tissue (P ¼ .054). These findings suggest that thymopoiesis is ongoing in the adult thymus and contributes to immune reconstitution in HIV-infected patients receiving HAART. Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of circulating CD4 + T lymphocytes (CD4 + cells). Treatment with highly active antiretroviral therapy (HAART) leads to some immunologic reconstitution, specifically, an increase in the number of CD4 + cells of both memory (CD45RO + )a nd naive (CD45RA + CD62L + ) phenotypes [1‐ 3]. The origin of the CD4 + cells that appear in the blood after initiation of treatment is still uncertain. Peripheral blood CD4 + cells can be replaced either by peripheral expansion of existing T cell clones or by production of new naive T cells from the thymus. However, it is known that the human thymus involutes with age, and its function as a T cell generator in adults has been assumed, therefore, to be limited [2, 4‐7]. Recently, thymic tissue has been detected in adult HIV-infected patients on computed tomographic (CT) scans, and it has been found that the size of this thymic tissue correlates with increases in naive CD4 + cells during the early phase of treatment with