Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro

Abstract

A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-l-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.

Mechanisms of protection induced by live attenuated simian immunodeficiency virus

“…The cellular arm of the immune response plays a critical role in the host's defense against viral infections and the CD8+ T-lymphocytes form an important part of this cellular immunity. The antiviral activity of CD8+ T-lymphocytes has been demonstrated in HIV-1-infected humans and chimpanzees [8,10,29]. Walker et al [54] demonstrated that CD8+ T-lymphocytes from asymptomatic HIV-infected individuals suppressed HIV replication in cultured PBMCs.…”

Immune Response of Mice Infected with Recombinant Vaccinia Viruses Carrying the HIV gag Gene

“…Although we measured here the splenic lymphocyte response to the p24 antigen as an indicator for evaluating cellular immunity, it is important to further clarify whether our recombinants, especially vac-gag/pol, are able to induce cytotoxic T cells against the cells expressing the gag antigen. If they have such an ability, we could expect that they interfere with the onset of AIDS from asymptomatic HIV carrier (15).…”

Abrogation of in vitro suppression of human immunodeficiency virus type 1 (HIV-1) replication mediated by CD8+ T lymphocytes of asymptomatic HIV-1 carriers by staphylococcal enterotoxin B and phorbol esters through induction of tumor necrosis factor alpha

“…We and others have shown that such CD8 ϩ cellmediated suppression is common in the PBMC of AC but rare in uninfected individuals or AIDS patients (15,23), implying that CD8 ϩ cell-mediated suppression may play an important role in maintaining an asymptomatic state. Furthermore, this protection is effective against not only endogenous but also exogenous infective laboratory strains of HIV-1 (15). Similar CD8 ϩ cell-mediated suppression of virus replication is ob-served in simian immunodeficiency virus-infected macaques and HIV-1-infected chimpanzees in vitro (4,16).…”

“…Removal of CD8 ϩ cells from the culture allows active virus replication in the remaining cells, indicating that CD8 ϩ T lymphocytes of AC suppress HIV-1 multiplication (37). We and others have shown that such CD8 ϩ cellmediated suppression is common in the PBMC of AC but rare in uninfected individuals or AIDS patients (15,23), implying that CD8 ϩ cell-mediated suppression may play an important role in maintaining an asymptomatic state. Furthermore, this protection is effective against not only endogenous but also exogenous infective laboratory strains of HIV-1 (15).…”