CD4+ T cell depletion, immune activation and increased production of regulatory T cells in the thymus of HIV-infected individuals.
Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation.
Bandera
Alessandra
A
Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milan-Bicocca, Monza, Italy. a.bandera@hsgerardo.org
Ferrario
Giulio
G
Saresella
Marina
M
Marventano
Ivana
I
Soria
Alessandro
A
Zanini
Fabio
F
Sabbatini
Francesca
F
Airoldi
Monica
M
Marchetti
Giulia
G
Franzetti
Fabio
F
Trabattoni
Daria
D
Clerici
Mario
M
Gori
Andrea
A
D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology / Q000821:virology*
D011948:Receptors, Antigen, T-Cell; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D020395:Receptors, Interleukin-7