Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome

Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo.

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

[2]  J. Manischewitz,et al.  Cytotoxic t cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients. , 1982, The New England journal of medicine.

[3]  M. Oldstone,et al.  Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo , 1984, Journal of virology.

[4]  T. Braciale,et al.  In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific , 1984, The Journal of experimental medicine.

[5]  R. Welsh,et al.  Adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo , 1985, The Journal of experimental medicine.

[6]  J. Levy,et al.  CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. , 1986, Science.

[7]  P. Kourilsky,et al.  Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo , 1987, Cell.

[8]  U. Koszinowski,et al.  CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity , 1987, Journal of virology.

[9]  R. Tedder,et al.  HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN TWO COHORTS OF HOMOSEXUAL MEN: NEUTRALISING SERA AND ASSOCIATION OF ANTI-GAG ANTIBODY WITH PROGNOSIS , 1987, The Lancet.

[10]  B. Walker,et al.  HIV-specific cytotoxic T lymphocytes in seropositive individuals , 1987, Nature.

[11]  B. Walker,et al.  HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. , 1988, Science.

[12]  B. Autran,et al.  Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans. , 1989, Journal of immunology.

[13]  R. Maziarz,et al.  Characterization of the T cell-mediated cellular cytotoxicity during acute infectious mononucleosis. , 1989, Journal of immunology.

[14]  D. Ho,et al.  Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. , 1989, The New England journal of medicine.

[15]  J L Sullivan,et al.  Severe herpesvirus infections in an adolescent without natural killer cells. , 1989, The New England journal of medicine.

[16]  B. Guy,et al.  Human immunodeficiency virus-specific cytotoxic responses of seropositive individuals: distinct types of effector cells mediate killing of targets expressing gag and env proteins , 1989, Journal of virology.

[17]  R. Koup,et al.  Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera , 1989, Journal of virology.

[18]  R. Koup,et al.  Detection of major histocompatibility complex class I-restricted, HIV-specific cytotoxic T lymphocytes in the blood of infected hemophiliacs. , 1989, Blood.

[19]  R. Young,et al.  Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. Martz,et al.  CTL: virus control cells first and cytolytic cells second? DNA fragmentation, apoptosis and the prelytic halt hypothesis. , 1989, Immunology today.

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

[22]  D. Watkins,et al.  A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. , 1989, Disease markers.

[23]  D. Ho,et al.  High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Albert,et al.  Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. , 1990, AIDS.

[25]  R. Welsh,et al.  Natural killer (NK) cell response to virus infections in mice with severe combined immunodeficiency. The stimulation of NK cells and the NK cell-dependent control of virus infections occur independently of T and B cell function , 1991, The Journal of experimental medicine.

[26]  S. J. Clark,et al.  High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. , 1991, The New England journal of medicine.

[27]  K. Murthy,et al.  Prevention of HIV infection by passive immunization with HIV immunoglobulin. , 1991, AIDS research and human retroviruses.

[28]  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.

[29]  D. Ho,et al.  Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. , 1991, The New England journal of medicine.

[30]  R. Weiss,et al.  Development of HIV‐1 group‐specific neutralizing antibodies after seroconversion , 1992, AIDS.

[31]  K. Ariyoshi,et al.  Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies? , 1992, The Lancet.

[32]  A CD4+ cytotoxic T-lymphocyte clone to a conserved epitope on human immunodeficiency virus type 1 p24: cytotoxic activity and secretion of interleukin-2 and interleukin-6 , 1992, Journal of virology.

[33]  W. Schleif,et al.  Prevention of HIV-1 infection in chimpanzees by gpl20 V3 domain-specific monoclonal antibody , 1992, Nature.

[34]  D. Ho,et al.  Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals , 1993, Journal of virology.

[35]  R. Welsh,et al.  High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response , 1993, The Journal of experimental medicine.

[36]  S. J. Clark,et al.  High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. , 1993, Science.

[37]  J. Safrit,et al.  hu-PBL-SCID mice can be protected from HIV-1 infection by passive transfer of monoclonal antibody to the principal neutralizing determinant of envelope gp120. , 1993, AIDS.

[38]  Anthony S. Fauci,et al.  HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease , 1993, Nature.

[39]  N. Letvin,et al.  Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys , 1993, Journal of virology.

[40]  D. Ho,et al.  Genotypic and phenotypic characterization of HIV-1 patients with primary infection. , 1993, Science.

[41]  Ashley T. Haase,et al.  Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS , 1993, Nature.

[42]  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.

[43]  D. Montefiori,et al.  Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques , 1994, Journal of virology.