Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy

ABSTRACT Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.

[1]  J. Altman,et al.  Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. , 1998, Immunity.

[2]  Philip J. R. Goulder,et al.  Phenotypic Analysis of Antigen-Specific T Lymphocytes , 1996, Science.

[3]  M A Nowak,et al.  Anti-viral drug treatment: dynamics of resistance in free virus and infected cell populations. , 1997, Journal of theoretical biology.

[4]  D. Cooper,et al.  Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir. , 1996, The Journal of infectious diseases.

[5]  B. Walker,et al.  An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Rowland-Jones,et al.  Strong Human Immunodeficiency Virus (HIV)-Specific Cytotoxic T-Lymphocyte Activity in Sydney Blood Bank Cohort Patients Infected with nef-Defective HIV Type 1 , 1999, Journal of Virology.

[7]  David Gray,et al.  Immunological Memory and Protective Immunity: Understanding Their Relation , 1996, Science.

[8]  D. Nixon,et al.  High frequency of memory and effector gag specific cytotoxic T lymphocytes in HIV seropositive individuals. , 1990, International immunology.

[9]  D. Ho,et al.  Toward HIV eradication or remission: the tasks ahead. , 1998, Science.

[10]  Kiyoshi Miwa,et al.  Identification of multiple HIV‐1 cytotoxic T‐cell epitopes presented by human leukocyte antigen B35 molecules , 1996, AIDS.

[11]  K. Parker,et al.  Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2. , 1992, Journal of immunology.

[12]  R. Phillips,et al.  Patterns of Immunodominance in HIV-1–specific Cytotoxic T Lymphocyte Responses in Two Human Histocompatibility Leukocyte Antigens (HLA)-identical Siblings with HLA-A*0201 Are Influenced by Epitope Mutation , 1997, The Journal of experimental medicine.

[13]  S. Rowland-Jones,et al.  Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  E. Rosenberg,et al.  Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. , 1997, Science.

[15]  D. Cooper,et al.  CD8+ lymphocyte responses to antiretroviral therapy of HIV infection. , 1996, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[16]  S. Rowland-Jones,et al.  Distinct Recognition of Non-Clade B Human Immunodeficiency Virus Type 1 Epitopes by Cytotoxic T Lymphocytes Generated from Donors Infected in Africa , 1999, Journal of Virology.

[17]  J Leibowitch,et al.  Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. , 1997, Science.

[18]  S. Rowland-Jones,et al.  Oligoclonal Expansions of CD8+ T Cells in Chronic HIV Infection Are Antigen Specific , 1998, The Journal of experimental medicine.

[19]  P. Klenerman,et al.  A functional and kinetic comparison of antiviral effector and memory cytotoxic T lymphocyte populations in vivo and in vitro , 1997, European journal of immunology.

[20]  G Shubinsky,et al.  The CD38 lymphocyte differentiation marker: new insight into its ectoenzymatic activity and its role as a signal transducer. , 1997, Immunity.

[21]  R. Detels,et al.  T-cell subset alterations in HIV-infected homosexual men: NIAID Multicenter AIDS cohort study. , 1989, Clinical immunology and immunopathology.

[22]  M A Nowak,et al.  Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. , 1998, Science.