Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy.
Cytotoxic T lymphocytes (CTLs) are an important defense against human immunodeficiency virus (HIV) type 1 but ultimately fail to control infection. To determine whether more efficient sustained immunity is induced by suppressing replication, the evolution of T cell phenotypes and HIV-specific CD8+ lymphocytes was prospectively investigated in 41 patients initiating combination therapy. Suppression of viremia to <200 copies/mL was associated with increases in naive cells (CD45RA+62L+) and declines in activated T cells (CD95+ cell counts and CD38+ HLA-DR+). HIV-specific tetramer-staining CD8+ T cells were detected in 6 of 10 HLA-A*0201-positive persons, which declined in 5 with treatment. CTL precursor frequencies were markedly consistent before and after treatment. Eight (72%) of 11 recognized > or =1 immunodominant epitope, representing either a new or an increased CTL response after treatment. Thus, activated CD8+ T cells, including those recognizing immunodominant epitopes, decline with combination therapy. However, the overall level of antigen-specific cells that are capable of differentiating into effectors remains stable, and the recognition of new epitopes may occur.
Seth
A
A
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Markee
J
J
Hoering
A
A
Sevin
A
A
Sabath
D E
DE
Schmitz
J E
JE
Kuroda
M J
MJ
Lifton
M A
MA
Hirsch
M S
MS
Collier
A C
AC
Letvin
N L
NL
McElrath
M J
MJ
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004359:Drug Therapy, Combination; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007150:Immunohistochemistry; D016130:Immunophenotyping; D019469:Indinavir / Q000494:pharmacology / Q000627:therapeutic use; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000032:analysis*; D011446:Prospective Studies; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1