Cytotoxic T lymphocytes against HIV

Walker, Bruce D.; Plata, Fernando

doi:10.1097/00002030-199003000-00001

Cited by 170 publications

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“…In contrast, CTL responses can be detected against viruses that establish latent or persistent infections, such as the herpesviruses (Yasukawa et al, 1989;Hickling et al, 1986;Rickinson et al, 1981) or human retroviruses (Walker & Plata, 1990;Kannagi et al, 1983;Mitsuya et at., 1983). Thus, the frequency of anti-VV CD8 + cells could drop to undetectable levels in the absence of periodic re-exposure to viral antigen through reinfection or reactivation of latent viruses.…”

Section: Short Communication 753mentioning

confidence: 99%

Class I major histocompatibility complex-restricted cytotoxic T cell responses to vaccinia virus in humans

Erickson¹,

Walker²

1993

Journal of General Virology

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Cytotoxic T lymphocyte (CTL) responses to vaccinia virus (VV) were studied in human subjects receiving smallpox vaccine by dermal scarification. After in vitro restimulation with VV, peripheral blood mononuclear cells (PBMCs) from three of six vaccinated subjects killed virus-infected target cells. W-specific, HLArestricted CTL activity was mediated primarily by CD8 + cells, although low levels of lytic activity by CD4 + cells were observed in some experiments. Two of the three responders had no history of exposure to VV prior to vaccination, whereas all three non-responders were vaccinated against smallpox during childhood. PBMCs from an additional three subjects who had received smallpox vaccine at least 20 years previously were negative for CTL activity. These data suggest that the duration of memory CTL populations against W in the peripheral blood is limited, and that pre-existing immunity to VV may interfere with boosting of the CTL response upon revaccination.The design of vaccines that will prime virus-specific class I major histocompatibility complex (MHC)-restricted T lymphocytes is complicated by the requirement for processing of antigen within the cytoplasm or endoplasmic reticulum (Morrison et al., 1986;Moore et al., 1988;Germain, 1986). Recombinant viruses deliver antigens efficiently into the class I antigen presentation pathway (Bennink & Yewdell, 1990;Moss, 1991), and thus have been proposed as vectors for vaccine delivery in humans. Infection of experimental animals with recombinant vaccinia virus (VV) vectors elicits cytotoxic T lymphocyte (CTL) populations that recognize VV antigens as well as heterologous protein(s) encoded by the virus (Bennink & Yewdell, 1990). However, attempts to detect class I MHC-restricted, VV-specific CTL in humans immunized against smallpox have been unsuccessful, even after revaccination with the virus (Perrin et aI., 1977;Graham et al., 1991). These data suggested that recombinant VV vectors may have a limited ability to prime CTL responses in humans (Graham et al., 1991).To gain an understanding of factors that influence priming and detection of anti-VV CTLs in humans, we undertook a study of virus-specific CTL activity in 10 laboratory staff volunteers. Smallpox vaccination is currently indicated for laboratory workers directly involved with orthopoxviruses such as VV (Anonymous, 1980). Accordingly, subjects 1 to 6 who work with recombinant VV vectors were immunized with 0.2 ml of dried smallpox vaccine (Dryvax, Wyeth) by dermal scarification (Table 1). Vaccine takes were confirmed by visual examination of the inoculation site. Four control subjects (7 to 10) who do not use recombinant VV vectors were not vaccinated.To generate VV-specific CTLs, peripheral blood mononuclear cells (PBMCs) from study subjects were enriched on Ficoll-Hypaque gradients and washed three times in PBS. PBMCs were then infected with VV (strain WR) at a multiplicity of 1 for 60 min. After one wash, 2 × 10 ~ cells/ml were cultured in 1.5 ml of RPMI 1640 medium supplemented with 10 % hea...

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Section: Short Communication 753mentioning

confidence: 99%

Class I major histocompatibility complex-restricted cytotoxic T cell responses to vaccinia virus in humans

Erickson¹,

Walker²

1993

Journal of General Virology

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“…Most seropositive individuals produce anti-HIV neutralizing antibodies [1,2] and antibodies capable of mediating antibody-dependent cellular cytotoxicity (ADCC) [3][4][5] and complement-dependent lysis of viral particles and infected cells [6,7]. Natural killer (NK) activity [8,9] and antigen-specific CD8^ cytotoxic T lymphocytes have also been demonstrated in HIV-infected individuals [10][11][12][13]. It is unclear if these responses play any role in controlling HIV replication in vivo and/or in the maintenance of the asymptomatic stage, but it is known that virus persists in the host throughout the course of clinical latency [14,15].…”

Section: Introductionmentioning

confidence: 99%

“…CD8^ T cells are known to exert their effector function by lysing infected cells in an MHCrestricted antigen-specific fashion [22]. Indeed, in HIV infection such classical anti-HIV cytotoxic T lymphocyte (CTL) activity has been demonstrated and characterized [10]. Tsubota et at.…”

Section: Introductionmentioning

confidence: 99%

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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“…High levels of HIV-specific CTL have been demonstrated in asymptomatic infected adults, which, in some studies, have been shown to be lost with disease progression. Others have suggested that HIVspecific CTL may have a pathogenic or deleterious effect (reviewed in [1][2][3]). …”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

Aldhous

Watret²,

Mok

et al. 1994

Clinical and Experimental Immunology

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SUMMARYHIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CDS lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any. between CTL activity and CDS subpopuiations. We have measured CTL activity against four HIV gene products (gag. tat. pal and en\) and expression of CD45RO, CD45RA. HLA-DR, CD29. S6F1, and CD57 surface markers on CDS cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HW-gag. -pot and -tat. and the other to HW-pot. All the HIV-infected and two uninfected children had abnormal proportions of CDS subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CDS subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CDS cells, an expansion of HLA-DR^ CD8 cells and a loss of CD45RA ' CDS cells.

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Cytotoxic T lymphocytes against HIV

Cited by 170 publications

References 0 publications

Class I major histocompatibility complex-restricted cytotoxic T cell responses to vaccinia virus in humans

Class I major histocompatibility complex-restricted cytotoxic T cell responses to vaccinia virus in humans

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

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

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