CD8+ T-cell-mediated non-cytolytic suppression of human immuno-deficiency viruses.
Major histocompatibility (MHC)-restricted cytotoxic T-lymphocytes (CTL) kill human immunodeficiency virus (HIV)-infected cells. In addition, activated CD8(+) T-lymphocytes from HIV-infected individuals suppress virus replication in vitro by producing antiviral factor (CAF). The effector mechanism(s) of CAF involves modulation of HIV gene transcription, is non-cytolytic and mediated in part by soluble antiviral factors. Initially, CAF activity was shown to be more vigorous in activated CD8(+) cells and cell free supernatants (SNs) from asymptomatic individuals compared to those with AIDS, suggesting a protective role in vivo. CAF-mediated suppression is also evident in animal models of immunodeficiency virus infection. Several soluble molecules that contribute to non-cytolytic virus suppression have been characterised, including alpha- and beta-chemokines and interleukin-16 (IL-16), but these are distinct from CAF. Two agents possessing certain CAF-like characteristics, modified antithrombin 111 (AT111) and the human alpha-defensins, have been described but their antiviral mechanisms are not fully understood. CAF-secretion may not be virus-specific as similar activity is found in activated CD8(+) cells/SNs from humans and chimpanzees seronegative for HIV-1. Recent data indicates that the secretion of CAF is MHC-restricted and both cytolytic and non-cytolytic mechanisms are mediated by CTL. If the latter is correct, a single appropriate stimulus could be used to enhance both effector mechanisms in vivo. This paper reviews research aimed at characterising HIV-suppressive factors and raises other questions that must be considered for the development of prophylactic and therapeutic strategies leading to the safe and effective control of HIV.
Vella
C
C
Department of Health and Human Sciences, London Metropolitan University, North London Campus, 166-220 Holloway Road, London N7 8DB, UK. c.vella@unl.ac.uk
Daniels
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RS
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
D000998:Antiviral Agents