Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in cerebrospinal fluid from infected persons with AIDS dementia complex.
AIDS dementia complex is a common neurologic disorder in later stages of HIV-1 infection. Because virus-specific CTL have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1-infected persons with various stages of AIDS dementia complex for the presence of HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were identified in the cerebrospinal fluid. These CTL were directed at epitopes within the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA class I Ag. In four of these subjects, virus-specific CTL were detected in higher numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a specific recruitment to or local induction within the nervous system. These studies demonstrate the presence of a vigorous and broadly directed CTL response to HIV-1 in the central nervous system of infected persons with AIDS dementia complex, and provide immunologic evidence of localized intrathecal infection. Although HIV-1-specific CTL may serve to inhibit viral replication in the central nervous system, the presence of a persistent CTL response in the central nervous system may also contribute to the neurologic disorders characteristic of HIV-1 infection.
Jassoy
C
C
Infectious Disease Unit, Massachusetts General Hospital, Boston 02114.
Johnson
R P
RP
Navia
B A
BA
Worth
J
J
Walker
B D
BD
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000276:immunology; D000595:Amino Acid Sequence; D002555:Cerebrospinal Fluid / Q000166:cytology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000235:genetics; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D008969:Molecular Sequence Data; D012194:RNA-Directed DNA Polymerase / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001616:beta-Galactosidase / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D000939:Epitopes; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D006680:HLA Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; D012194:RNA-Directed DNA Polymerase; D001616:beta-Galactosidase