title: Progression of human immunodeficiency virus disease is associated with increasing disruptions within the CD4+ T cell receptor repertoire.
abstract: The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.2%, 95% CI, 2.3%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jgbanacloc@nih.gov
authors.forename: J C
authors.initials: JC
authors.lastname: Gea-Banacloche
authors.forename: E E
authors.initials: EE
authors.lastname: Weiskopf
authors.forename: C
authors.initials: C
authors.lastname: Hallahan
authors.forename: J C
authors.initials: JC
authors.lastname: López Bernaldo de Quirós
authors.forename: M
authors.initials: M
authors.lastname: Flanigan
authors.forename: J M
authors.initials: JM
authors.lastname: Mican
authors.forename: J
authors.initials: J
authors.lastname: Falloon
authors.forename: M
authors.initials: M
authors.lastname: Baseler
authors.forename: R
authors.initials: R
authors.lastname: Stevens
authors.forename: H C
authors.initials: HC
authors.lastname: Lane
authors.forename: M
authors.initials: M
authors.lastname: Connors
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta