Thymopoiesis in HIV-Infected Adults after Highly Active Antiretroviral Therapy

Abstract

The thymus of HIV-seropositive patients can enlarge as CD4⁺ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV-infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4⁺ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4⁺ CD45RA⁺ CD62L⁺ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4⁺ T cell counts increased from approximately 60/mm³ to 552/mm³ and 750/mm³ for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD45RA⁺ CD62L⁺ CD4⁺ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4⁺ T lymphopenia.