A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes.

Tsubota, Hiroshi; Lord, Carol I.; Watkins, David I.; Morimoto, Chikao; Letvin, Norman L.

doi:10.1084/jem.169.4.1421

Cited by 243 publications

(110 citation statements)

References 24 publications

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“…The potential role of CD8 + cells in preventing virus production after acute infection of PBMC of asymptomatic individuals is supported by previous findings that these cells have anti-HIV suppressing activity (Brinchmann et al, 1990;Tsubota et al, 1989;Walker et al, 1986Walker et al, , 1991a. Moreover, in an earlier study of superinfection, Kannagi et al (1990) demonstrated in preliminary studies that CD8 + cells from asymptomatic individuals do not lyse CD4 + cells infected with an exogenous virus, thus suggesting a suppressing mechanism.…”

Section: Discussionsupporting

confidence: 66%

CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals suppress superinfection of their peripheral blood mononuclear cells

Barker

Bossart²,

Locher³

et al. 1996

Journal of General Virology

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Section: Discussionsupporting

confidence: 66%

CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals suppress superinfection of their peripheral blood mononuclear cells

Barker

Bossart²,

Locher³

et al. 1996

Journal of General Virology

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“…There is controversy regarding the mechanism of CD8+ T cell-mediated inhibition of HIV replication in vitro. It has been argued that CD8^ cells mediate suppression of HIV replication in vitro without killing CD4ĉ ells [28], but others [17] have suggested that this effect is mediated by CD8^ cytotoxicity. Zarling et al [24] reported that CD8^ T cells from HIV-infected individuals, but not chimpanzees, have circulating cytotoxic T lymphocytes that lyse activated autologous HIV-infeeted and -uninfected CD4T cells.…”

Section: Discussionmentioning

confidence: 99%

“…While it is known that this activity is not mediated by CD16^/CD8^ NK cells [17], the mechanism by which CD8+ cells from HIV-infected individuals inhibit viral replication in vitro is subject to controversy. CD8^ T cells are known to exert their effector function by lysing infected cells in an MHCrestricted antigen-specific fashion [22].…”

Section: Introductionmentioning

confidence: 99%

“…HIV-infected individuals also possess CD8^ lymphocytes capable of suppressing HIV rephcation in vitro [16][17][18]. This was initially shown in healthy HI V^ individuals whose cultured peripheral blood mononuclear cells (PBMC) did not produce infectious virus.…”

Section: Introductionmentioning

confidence: 99%

“…Further, the ability of these cells lo inhibit virus replication was blocked with MoAbs that interfered with physical contact between CD8"^ lymphocytes and their target cells [17]. Landay el al.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and clinical stage of disease

Gómez

Smaill

Rosenthal

1994

Clinical and Experimental Immunology

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SUMMARY We sought to evaluate the relationship of CD8+ T cell‐mediated inhibition of autologous HIV replication in vitro to disease stage in HIV+ individuals. Depletion of CD8+ T cells from peripheral blood lymphocytes of 16 HIV+ subjects increased the percentage of virus‐producing cultures from 56% to 81%. CD4+ T cells were purified from 52 HIV+ individuals and cultured alone or in the presence of autologous CD8+ T cells. In 13 (25%) subjects HIV replication was only detected in the absence of CD8+ T cells (inhibition positive); in 26 (50%) viral replication occurred both in the absence and presence of CD8+ cells (inhibition negative). In the remaining 13 (25%) subjects, CD8+ T cell‐mediated inhibitory activity could not be evaluated because stimulation of their purified CD4+ T cells did not result in p24 production. In some virus culture‐negative individuals, the inability to demonstrate HIV replication was due to the presence of low numbers of CD8+ T cells that co‐purified with CD4+ T cells. Detection of inhibitory CD8+ T cells was associated with significantly higher CD4 counts and better clinical status compared with inhibition‐negative subjects. These results demonstrate that CD8+ T cell‐mediated inhibition of HIV replication correlates with disease stage, and thus may play a role in preventing disease progression. CD8+ T cells did not inhibit autologous HIV replication across a semipermeable membrane. Further, the ability of CD8+ T cells to prevent HIV replication did not correlate with lysis of autologous CD4+ T cells. Thus, CD8+ T cells inhibited autologous HIV replication in vitro through a contact mediated non‐lytic mechanism.

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Isolation and Quantitation of HIV in Peripheral Blood

Koup

Poli

et al. 1993

CP in Immunology

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Quantitation of replication-competent human immunodeficiency virus (HIV) in peripheral blood of infected individuals is critical for investigations of HIV pathogenesis and therapy. In this unit, the basic protocol determines the HIV titer in seropositive blood by measuring the tissue culture infectious dose (TCID) by an end-point dilution method. A second basic protocol utilizes the PHA-stimulated T cell blasts (activated T cells) in co-culture with PBMC as described in the first basic protocol for the short-term growth of HIV in vitro. An Alternate Protocol describes the accumulative method of determining 50% tissue culture infectious dose (TCID(50)) of HIV using the Reed-Muench equation when multiple replicates of a given sample are employed in the assay. A consequence of HIV infection is the depletion of CD4(+) target cells, evidenced by syncytia formation or single-cell death; two support protocols detail the evaluation of these cytopathic effects.

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A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes.

Cited by 243 publications

References 24 publications

CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals suppress superinfection of their peripheral blood mononuclear cells

CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals suppress superinfection of their peripheral blood mononuclear cells

Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and clinical stage of disease

Isolation and Quantitation of HIV in Peripheral Blood

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