HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies.
Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4+ T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4+ T cells increased only if they were present before initiation of therapy. Disruptions of the CD4+ TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4+ T cells and disruptions of the CD4+ T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies.
Connors
M
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
Kovacs
J A
JA
Krevat
S
S
Gea-Banacloche
J C
JC
Sneller
M C
MC
Flanigan
M
M
Metcalf
J A
JA
Walker
R E
RE
Falloon
J
J
Baseler
M
M
Feuerstein
I
I
Masur
H
H
Lane
H C
HC
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000097:blood; D010641:Phenotype; D012333:RNA, Messenger / Q000097:blood; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014430:Twins, Monozygotic
D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019469:Indinavir; D017493:Leukocyte Common Antigens