Longitudinal analysis of T-cell receptor gene use by CD8(+) T cells in early human immunodeficiency virus infection in patients receiving highly active antiretroviral therapy.
The effects of early antiretroviral therapy on the peripheral CD8(+) T-cell population were assessed by sequentially determining the T-cell receptor (TCR) repertoire complexity in a cohort of 15 individuals recently diagnosed with human immunodeficiency virus infection. Analysis was based on quantitative TCR variable B gene (TCRBV) usage and complementary-determining region 3 length assessment. Repertories were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. Early administration of highly active antiretroviral therapy has a positive effect on the preservation and homeostasis of the CD8(+) cell repertoire. Nevertheless, differences from average baseline and control TCR profiles and initial development of repertoire perturbations were observed. The findings suggest that additional therapeutic protocols will be required during primary infection to significantly prevent long-term erosion of the T-cell-mediated immune response.
Schito
A M
AM
Departments of Neurology, Epidemiology and Biostatistics, and Medicine, and the Positive Health Program HIV Section, University of California at San Francisco, CA 94143-0435, USA.
Vittinghoff
E
E
Hecht
F M
FM
Elkins
M K
MK
Kahn
J O
JO
Levy
J A
JA
Oksenberg
J R
JR
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D022801:Complementarity Determining Regions / Q000032:analysis / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000187:drug effects; D019672:Genes, T-Cell Receptor / Q000187:drug effects / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D044469:Racial Groups; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents; D022801:Complementarity Determining Regions; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta