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

Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

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

Blood ◽

10.1182/blood.v73.7.1909.1909 ◽

1989 ◽

Vol 73 (7) ◽

pp. 1909-1914 ◽

Cited By ~ 47

Author(s):

RA Koup ◽

JL Sullivan ◽

PH Levine ◽

D Brettler ◽

A Mahr ◽

...

Keyword(s):

T Lymphocytes ◽

Mhc Class I ◽

Cytotoxic T Lymphocytes ◽

Mononuclear Cells ◽

Nk Cell ◽

Class I ◽

Gene Products ◽

Major Histocompatibility ◽

Peripheral Blood Mononuclear ◽

Hiv 1

Abstract Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

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Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2000.0646 ◽

2000 ◽

Vol 355 (1400) ◽

pp. 1085-1092 ◽

Cited By ~ 24

Author(s):

Franziska Lechner ◽

John Sullivan ◽

Hans Spiegel ◽

Douglas F. Nixon ◽

Belinda Ferrari ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Hepatitis C Virus ◽

Hepatitis C ◽

T Lymphocytes ◽

Mhc Class I ◽

Cytotoxic T Lymphocytes ◽

Class I ◽

Major Public Health Problem ◽

Major Histocompatibility ◽

Histocompatibility Complex

Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV–infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this ‘CTL failure’ are discussed.

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Virus-Specific Cytotoxic T Lymphocytes in Human Immunodeficiency Virus Type 1-Infected Chimpanzees

Journal of Virology ◽

10.1128/jvi.73.8.7065-7069.1999 ◽

1999 ◽

Vol 73 (8) ◽

pp. 7065-7069 ◽

Cited By ~ 4

Author(s):

Sampa Santra ◽

Patricia N. Fultz ◽

Norman L. Letvin

Keyword(s):

Human Immunodeficiency Virus ◽

T Lymphocytes ◽

Cytotoxic T Lymphocytes ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Chimpanzees have been important in studies of human immunodeficiency virus type 1 (HIV-1) pathogenesis and in evaluation of HIV-1 candidate vaccines. However, little information is available about HIV-1-specific cytotoxic T lymphocytes (CTL) in these animals. In the present study, in vitro stimulation of peripheral blood mononuclear cells (PBMC) from infected chimpanzees with HIV-1 Gag peptides was shown to be a sensitive, reproducible method of expanding HIV-1-specific CD8+ effector CTL. Of interest, PBMC from two chimpanzees had CTL activity against Gag epitopes also recognized by major histocompatibility complex class I-restricted CTL from HIV-1-infected humans. The use of peptide stimulation will help to clarify the role of CTL in vaccine-mediated protection and HIV-1 disease progression in this important animal model.

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