Association between Virus-Specific Cytotoxic T-Lymphocyte and Helper Responses in Human Immunodeficiency Virus Type 1 Infection

ABSTRACT Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development.

[1]  I. Lefkovits Limiting Dilution Analysis , 1979 .

[2]  H. Waldmann,et al.  Limiting Dilution Analysis of Cells in the Immune System , 1980 .

[3]  Fazekas de St Groth The evaluation of limiting dilution assays. , 1982, Journal of immunological methods.

[4]  S. Buchbinder,et al.  Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics. , 1991, The Journal of infectious diseases.

[5]  R. Koup,et al.  Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities , 1991, The Journal of experimental medicine.

[6]  S. Riddell,et al.  Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. , 1991, Blood.

[7]  John W. Mellors,et al.  Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences , 1997 .

[8]  R. Swanstrom,et al.  Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo , 1993, Journal of virology.

[9]  X. Jin,et al.  Quantitative analysis of the human immunodeficiency virus type 1 (HIV- 1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein- Barr virus in late disease , 1993, The Journal of experimental medicine.

[10]  G. Shaw,et al.  Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection , 1994, Journal of virology.

[11]  B. Walker,et al.  Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire , 1994, The Journal of experimental medicine.

[12]  R. Young,et al.  Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1 , 1994, The Journal of experimental medicine.

[13]  D. Ho,et al.  Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome , 1994, Journal of virology.

[14]  R. Ahmed,et al.  CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection , 1994, Journal of virology.

[15]  H. Schuitemaker,et al.  Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics , 1995, The Journal of experimental medicine.

[16]  R. Detels,et al.  Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-HIV CD8+ lymphocyte activity. , 1995, The Journal of infectious diseases.

[17]  H. Clifford Lane,et al.  Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression , 1995, Nature Medicine.

[18]  C. Rinaldo,et al.  High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors , 1995, Journal of virology.

[19]  B. Walker,et al.  Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. , 1996, AIDS research and human retroviruses.

[20]  M. V. von Herrath,et al.  CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge , 1996, Journal of virology.

[21]  B. Walker,et al.  Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. , 1996, Journal of immunology.

[22]  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.

[23]  J. Moore,et al.  Differential regulation of the antibody responses to Gag and Env proteins of human immunodeficiency virus type 1 , 1997, Journal of virology.

[24]  R P Johnson,et al.  Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms , 1997, Journal of virology.

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

[26]  B. Korber,et al.  Human retroviruses and AIDS 1997 , 1997 .

[27]  J. Altman,et al.  Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function , 1998, The Journal of experimental medicine.

[28]  R P Johnson,et al.  Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection. , 1998, The Journal of clinical investigation.

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

[30]  Spyros A. Kalams,et al.  The Critical Need for CD4 Help in Maintaining Effective Cytotoxic T Lymphocyte Responses , 1998, The Journal of experimental medicine.

[31]  H. Schuitemaker,et al.  Longitudinal analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte responses: a predominant gag-specific response is associated with nonprogressive infection. , 1998, The Journal of infectious diseases.

[32]  M. Nowak,et al.  Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy , 1999, Journal of Virology.