Quantification of CD8+ T lymphocytes responsive to human immunodeficiency virus (HIV) peptide antigens in HIV-infected patients and seronegative persons at high risk for recent HIV exposure.

The combination of a tumor necrosis factor (TNF)-alpha enzyme-linked immunospot (ELISPOT) assay and computer-assisted video image analysis was used to detect and quantitate in peripheral blood CD8+ T cells reactive with known human immunodeficiency virus type 1 (HIV-1) peptide antigens presented by HLA-A2 or HLA-A3. T lymphocyte responsiveness to at least one HIV peptide was found in 10 (83%) of 12 HIV-1-infected patients and in 5 (45%) of 11 persons who had no serologic and virologic signs of HIV infection but who were at high risk for recent sexual exposure to HIV-1. CD8+ T cells responding to HIV-1 peptides were observed in none of 11 HIV-seronegative donors without a history of HIV exposure. ELISPOT assays are relatively fast and easy to perform and appear to reliably detect T cell reactivity due to previous exposure to HIV. These findings support the use of the ELISPOT assay for monitoring T cell responsiveness to HIV peptides.

[1]  K. Steimer,et al.  Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). , 1985, Science.

[2]  M. Serrano,et al.  A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma , 1995, Science.

[3]  S. Rowland-Jones,et al.  HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women , 1995, Nature Medicine.

[4]  B. Guy,et al.  Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein. , 1991, Journal of immunology.

[5]  S. H. van der Burg,et al.  Induction of a primary human cytotoxic T‐lymphocyte response against a novel conserved epitope in a functional sequence of HIV‐1 reverse transcriptase , 1995, AIDS.

[6]  M. Bednarek,et al.  The minimum peptide epitope from the influenza virus matrix protein. Extra and intracellular loading of HLA-A2. , 1991, Journal of immunology.

[7]  J. Berzofsky,et al.  ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. , 1995, The Journal of clinical investigation.

[8]  P. Earl,et al.  Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  C. Griscelli,et al.  Cytotoxic T lymphocyte responses in the peripheral blood of children born to human immunodeficiency virus‐1‐infected mothers , 1992, European journal of immunology.

[10]  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.

[11]  D. Nixon,et al.  Cytotoxic T-cell recognition of HIV proteins and peptides. , 1991, AIDS.

[12]  A. Lohse,et al.  Detection and quantification of blood-derived CD8+ T lymphocytes secreting tumor necrosis factor alpha in response to HLA-A2.1-binding melanoma and viral peptide antigens. , 1996, Journal of immunological methods.

[13]  R. Siliciano,et al.  Induction of a major histocompatibility complex class I-restricted cytotoxic T-lymphocyte response to a highly conserved region of human immunodeficiency virus type 1 (HIV-1) gp120 in seronegative humans immunized with a candidate HIV-1 vaccine , 1994, Journal of virology.

[14]  J. Berzofsky,et al.  Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1. , 1992, The Journal of infectious diseases.

[15]  N. Leister,et al.  The use of computer-assisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor alpha spots in response to peptide antigens. , 1997, Journal of immunological methods.

[16]  J. Safrit,et al.  The immunology of primary HIV infection: which immune responses control HIV replication? , 1995, Current opinion in immunology.