T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy.
Impairment of T-cell renewal has been proposed as contributing to CD4(+) T-cell depletion in persons infected with human immunodeficiency virus-1. We analyzed the T-cell development capacity of progenitors using fetal thymus organ culture. Those who progressed to AIDS had a dramatic loss in T-cell development capacity shortly after seroconversion. In contrast, long-term nonprogressors retained progenitor capacity 8 years after seroconversion. Approximately 70% of patients experienced an improvement in T-cell development capacity after receiving 6 months of potent antiretroviral therapy. Improvement in T-cell development in fetal thymus organ culture correlated with an increase in the number of naive CD4(+) T cells in peripheral blood. Numbers of progenitors in blood and bone marrow after seroconversion or during therapy did not correlate with the change observed in T-cell development capacity. These data provide evidence that HIV-1 infection can interfere with T-cell renewal at the level of the progenitor cell. Interference with T-cell renewal may contribute to CD4(+) T-cell depletion.
Clark
D R
DR
Department of Clinical Viro-Immunology, Laboratory for Experimental and Clinical Immunology, CLB, Sanquin Blood Supply Foundation, the National AIDS Therapy Evaluation Center, the Division of Infectious Diseases, Amesterdam, The Netherlands.
Repping
S
S
Pakker
N G
NG
Prins
J M
JM
Notermans
D W
DW
Wit
F W
FW
Reiss
P
P
Danner
S A
SA
Coutinho
R A
RA
Lange
J M
JM
Miedema
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D016654:Genes, RAG-1; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*
D019380:Anti-HIV Agents; D018398:Homeodomain Proteins; C064658:RAG-1 protein