Transient renewal of thymopoiesis in HIV-infected human thymic implants following antiviral therapy.
Stem cell gene therapy strategies for AIDS require that differentiation-inducing stromal elements of HIV-infected individuals remain functionally intact to support the maturation of exogenous progenitor cells into mature CD4+ cells. To investigate the feasibility of stem cell reconstitution strategies in AIDS, we used the SCID-hu mouse to examine the ability of HIV-infected CD4+ cell-depleted human thymic implants to support renewed thymopoiesis. Here we report that following treatment of these implants with antiretroviral drugs, new thymopoiesis is initiated. This suggests that antiviral therapies might allow de novo production of T lymphocytes and provides support for the concept of therapeutic strategies aimed at reconstitution of the peripheral CD4+ T-cell compartment.
Withers-Ward
E S
ES
Department of Microbiology and Immunology, UCLA School of Medicine 90095, USA.
Amado
R G
RG
Koka
P S
PS
Jamieson
B D
BD
Kaplan
A H
AH
Chen
I S
IS
Zack
J A
JA
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D008212:Lymphocyte Depletion; D008782:Methylurea Compounds / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification; D011725:Pyridines / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013950:Thymus Gland / Q000276:immunology / Q000637:transplantation*; D014183:Transplantation, Heterologous; D014633:Valine / Q000031:analogs & derivatives; D015215:Zidovudine / Q000627:therapeutic use
D015703:Antigens, CD; D018952:Antigens, CD34; D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D008782:Methylurea Compounds; D011725:Pyridines; D015215:Zidovudine; C079555:Abbott 77003; D014633:Valine; D016049:Didanosine