Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene expression after 1 year of highly active antiretroviral therapy.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene expression after 1 year of highly active antiretroviral therapy.

AIDS. 1999 Feb 4;13(2):185-94. Unique Identifier : AIDSLINE MED/99217474
Martinon F; Michelet C; Peguillet I; Taoufik Y; Lefebvre P; Goujard C; Guillet JG; Delfraissy JF; Lantz O; ICGM-INSERM U445, Hopital Cochin, Paris, France.

Abstract: OBJECTIVES: To examine T-cell repertoire modifications, the evolution of T-helper (TH)1/TH2 cytokine imbalance and modifications in chemokine receptor expression when the viral load is decreased by 2-3 log10 copies/ml under highly active antiretroviral therapy (HAART). DESIGN: Sixteen patients previously treated with zidovudine and lamivudine, with CD4 cells below 300 x 10(6)/l and viraemia above 30000 copies/ml were treated by saquinavir and ritonavir together with both reverse transcriptase (RT) inhibitors (ANRS 069 trial). T-cell repertoire, chemokine receptor and lymphokine expression were studied from peripheral blood mononuclear cells sampled at weeks 0, 24 and 48. METHODS: T-cell repertoire study was carried out using the Immunoscope method. Interleukin (IL)-12 receptor beta2, CC-chemokine receptor (CCR)-3, CXC-chemokine receptor-4 and CCR-5 expression in CD4+ cells was measured by kinetic quantitative PCR and IL-2, IL-4, IL-10, IL-13, interferon (IFN)-gamma were measured using a quantitative RT-PCR assay with homologous internal standards. RESULTS: Repertoire alterations were more frequent in CD4- than in CD4+ cells and persisted despite undetectable viraemia. Increased CCR-3 expression and spontaneous IFN-gamma as well as mitogenic induced IL-13 were observed at baseline and decreased slightly under HAART. CONCLUSION: The CD8+ cell repertoire alterations were profound, whereas the CD4+ cell alterations were moderate and both persisted unchanged under HAART. The TH1/TH2 imbalance was more related to TH2 over-expression than to TH1 deficiency and persisted for at least 1 year under HAART.

Keywords: JOURNAL ARTICLE Adult Anti-HIV Agents/*THERAPEUTIC USE Cytokines/*GENETICS CD4-Positive T-Lymphocytes/*IMMUNOLOGY Female Gene Expression Human HIV Infections/DRUG THERAPY/GENETICS/*IMMUNOLOGY HIV Protease Inhibitors/*THERAPEUTIC USE Interferon Type II/GENETICS Interleukin-10/GENETICS Interleukin-13/GENETICS Interleukin-2/GENETICS Interleukin-4/GENETICS Lamivudine/THERAPEUTIC USE Longitudinal Studies Male Receptors, Chemokine/*GENETICS Receptors, CCR5/GENETICS Receptors, CXCR4/GENETICS Receptors, Interleukin/GENETICS Reverse Transcriptase Inhibitors/*THERAPEUTIC USE Ritonavir/THERAPEUTIC USE RNA, Messenger Saquinavir/THERAPEUTIC USE Support, Non-U.S. Gov't Zidovudine/THERAPEUTIC USE
990830
A9981014

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