Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy.
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/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ 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.
Markert
M L
ML
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Alvarez-McLeod
A P
AP
Sempowski
G D
GD
Hale
L P
LP
Horvatinovich
J M
JM
Weinhold
K J
KJ
Bartlett
J A
JA
D'Amico
T A
TA
Haynes
B F
BF
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000502:physiology; D016131:Lymphocyte Subsets; D008297:Male; D011859:Radiography; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000000981:diagnostic imaging / Q000276:immunology
D016207:Cytokines