Detection of major histocompatibility complex class I-restricted, HIV- specific cytotoxic T lymphocytes in the blood of infected hemophiliacs

Koup, Richard A.; Sullivan, John L.; Levine, Peter H.; Brettler, Doreen B.; Mahr, Anna; Mazzara, Gail P.; McKenzie, Sara; Panicali, Dennis

doi:10.1182/blood.v73.7.1909.1909

Cited by 79 publications

(31 citation statements)

References 34 publications

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“…The intensities of FIV-specific cytotoxic responses by PBMC with or without a brief stimulation with the T-cell mitogen ConA and IL-2 were lower than those reported for PBMC or ConA blasts of HIV-seropositive humans (14,19,22,30,46,48) or SIV-infected primates (26-28). In addition, we were unable to detect cytotoxic T-cell responses in lymphoblasts sampled before 7 weeks postinfection, whereas SIV-specific cytotoxicity mediated by PBMC was detected as early as 2 weeks after infection of macaques (26).…”

Section: Discussioncontrasting

confidence: 55%

“…Therefore the higher levels of lentivirus-specific CTL activity in humans and simians than in cats may be due to a higher frequency of lentivirusreactive CTL precursors in humans and nonhuman primates. Alternatively, the FIV-specific CTL may be directed against antigens other than envelope proteins, since gag-specific CTL precursor populations have not been detected in HIVseronegative individuals (9, 21,22).…”

Section: Discussionmentioning

confidence: 99%

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Induction of feline immunodeficiency virus-specific cytolytic T-cell responses from experimentally infected cats

Song

Collisson

Billingsley

et al. 1992

J Virol

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We have examined the in vitro induction and activity of feline immunodeficiency virus (FMV)-specific cytolytic T cells obtained from cats experimentally infected for 7 to 17 weeks or 20 to 22 months with the Petaluma isolate of FIV. Normal or FIV-infected autologous and allogeneic T lymphoblastoid cells were used as target cells in chromium-51 or indium-ill release assays. When effector cells consisted of either fresh peripheral blood mononuclear cells or concanavalin A-and interleukin-2-stimulated cells, only low levels of cytotoxicity were observed. However, the levels of FIV-specific cytotoxicity were consistently higher in both groups of cats following in vitro stimulation of the effector cells with irradiated, FIV-infected autologous T lymphoblastoid cells and interleukin-2. The effector cells lysed autologous but not allogeneic FIV-infected target cells and were composed predominantly of CD8+ T cells, indicating that the FIV-specific cytotoxicity measured in this system is mediated by CD8+, major histocompatibility complex class I-restricted T cells. These studies show that FIV-specific cytolytic T cells can be detected as early as 7 to 9 weeks postinfection, and they define a system to identify virus-encoded epitopes important in the induction of protective immunity against lentiviruses. Feline immunodeficiency virus (FIV) is currently considered a valuable small-animal model for human immunodeficiency virus (HIV)-induced AIDS in humans (2, 4, 8, 11, 17, 24, 33, 39, 43, 53-55). The observation that humans may be infected with HIV-1 for long periods without clinical illness suggests that a natural immune mechanism must be capable of inhibiting the spread of viral infection (49). Cell-mediated immune mechanisms, especially HIV-1-specific cellular cytotoxicity, may be particularly important in host defense against this virus by destroying virus-infected cells (12, 16, 25, 34, 35, 46) and suppressing viral replication (18, 44, 50). Cytotoxic T lymphocytes (CTL) directed against HIV-1 have been detected in HIV-infected humans

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Induction of feline immunodeficiency virus-specific cytolytic T-cell responses from experimentally infected cats

Song

Collisson

Billingsley

et al. 1992

J Virol

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“…However, the present study of 36 HIV‐infected individuals did not shown an association between the levels of HIV specific‐CTL activity and CD4 count, viral load or risk of death. Our results are in agreement with several studies that report no correlation between anti‐HIV CTL activity and CD4 + cells [ 9–12], CD8 + cells [ 13] or disease stage [ 14, 15]. In another study, which included 57 HIV‐1‐infected homosexual men, Rinaldo et al .…”

Section: Discussionsupporting

confidence: 93%

Bulk Culture Levels of Specific Cytotoxic T‐Cell Activity Against HIV‐1 Proteins are not Associated with Risk of Death

Aladdin

Ullum

et al. 1999

Scand J Immunol

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The ability of cytotoxic T lymphocytes (CTL) to control and influence the outcome of human immunodeficiency virus (HIV) infection is not fully understood. The association between HIV-CTL activity and disease progression was evaluated prospectively in 36 HIV-1-infected individuals with a median follow-up of 3.0 years. HIV-CTL activity was measured in a 4 h Cr* release assay using autologous target cells expressing HIV-1 BRU isolate gene products (gp-120, gag, pol, nef) and a bulk culture of autologous effector cells. The CD4 count was measured at enrolment and plasma HIV RNA was measured retrospectively. The present study failed to support the hypothesis that HIV-CTL activity, as measured using the present method, is important in reducing the risk of death in HIV-infected individuals. However, using other approaches and methods could possibly yield other conclusions, and further prospective studies are needed to examine the relationship between CTL and disease progression.

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“…All CTL assays were conventional 5-h 51Cr release assays as described in Littaua et al (24) and Koup et al (23). Briefly, autologous and allogeneic B-LCL target cells infected at a multiplicity of infection of 5 to 10 PFU per cell 16 h prior to the assay were 51Cr labeled by incubation of 106 cells with 100 ,uCi of Na" CrO4 (Amersham, Arlington Heights, Ill.) in a 100-pul volume for 1 h at 37°C, washed four times, and resuspended in R10 medium at 105 cells per ml.…”

mentioning

confidence: 99%

Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection

Borrow

Lewicki

Hahn

et al. 1994

J Virol

1,726

423

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Human immunodeficiency virus type 1 (HIV-1) Env-, Gag-, Pol-, Nef-, and Tat-specific cytotoxic Tlymphocyte (CTL) activities were quantitated temporally in five patients with symptomatic primary HIV-1 infection. A dominant CD8+-mediated, major histocompatibility complex class I-restricted CTL response to the HIV-1 envelope glycoprotein, gpl60, was noted in four of the five patients studied. The level of HIV-1-specific CTL activity in the five patients paralleled the efficiency of control of primary viremia. Patients who mounted strong gpl60-specific CTL responses showed rapid reduction of acute plasma viremia and antigenemia, while in contrast, primary viremia and antigenemia were poorly controlled in patients in whom virus-specific CTL activity was low or undetectable. These results suggest that HIV-1-specific CTL activity is a major component of the host immune response associated with the control of virus replication following primary HIV-1 infection and have important implications for the design of antiviral vaccines.

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Detection of major histocompatibility complex class I-restricted, HIV- specific cytotoxic T lymphocytes in the blood of infected hemophiliacs

Cited by 79 publications

References 34 publications

Induction of feline immunodeficiency virus-specific cytolytic T-cell responses from experimentally infected cats

Induction of feline immunodeficiency virus-specific cytolytic T-cell responses from experimentally infected cats

Bulk Culture Levels of Specific Cytotoxic T‐Cell Activity Against HIV‐1 Proteins are not Associated with Risk of Death

Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection

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