Proliferation of double-negative (CD4−CD8−) T cells bearing T-cell receptor-αβ in a haemophiliac with human immunodeficiency virus type 1 infection and factor VIII inhibitor: functional properties of double-negative T-cell receptor-αβ+T cells

1991 ◽  
Vol 79 (3) ◽  
pp. 372-376 ◽  
Author(s):  
Masaki Yasukawa ◽  
Takaaki Hato ◽  
Mitsuru Matsumoto ◽  
Kiyonori Takada ◽  
Shigeru Fujita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
Factor Viii Inhibitor ◽  
Double Negative ◽  
Immunodeficiency Virus ◽  
Viii Inhibitor

scholarly journals Alterations in T-Cell Receptor Vβ Repertoire of CD4 and CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Children

2003 ◽  
Vol 10 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Monica Kharbanda ◽  
Thomas W. McCloskey ◽  
Rajendra Pahwa ◽  
Mei Sun ◽  
Savita Pahwa
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Chronic Phase ◽  
Cell Receptor ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus

ABSTRACT Perturbations in the T-cell receptor (TCR) Vβ repertoire were assessed in the CD4 and CD8 T lymphocytes of human immunodeficiency virus (HIV)-infected children who were receiving therapy during the chronic phase of infection by flow cytometry (FC) and PCR analysis. By FC, representation of 21 TCR Vβ subfamilies was assessed for an increased or decreased percentage in CD4 and CD8 T cells, and by PCR, 22 TCR Vβ subfamilies of CD4 and CD8 T cells were analyzed by CDR3 spectratyping for perturbations and reduction in the number of peaks, loss of Gaussian distribution, or clonal dominance. The majority of the TCR Vβ subfamilies were examined by both methods and assessed for deviation from the norm by comparison with cord blood samples. The CD8-T-lymphocyte population exhibited more perturbations than the CD4 subset, and clonal dominance was present exclusively in CD8 T cells. Of the 55 total CD8-TCR Vβ families classified with clonal dominance by CDR3 spectratyping, only 18 of these exhibited increased expression by FC. Patients with high numbers of CD8-TCR Vβ families with decreased percentages had reduced percentages of total CD4 T cells. Increases in the number of CD4-TCR Vβ families with increased percentages showed a positive correlation with skewing. Overall, changes from normal were often discordant between the two methods. This study suggests that the assessment of HIV-induced alterations in TCR Vβ families at cellular and molecular levels yields different information and that our understanding of the immune response to HIV is still evolving.

scholarly journals T-Cell Receptor-Mediated Anergy of a Human Immunodeficiency Virus (HIV) gp120-Specific CD4+ Cytotoxic T-Cell Clone, Induced by a Natural HIV Type 1 Variant Peptide

2000 ◽  
Vol 74 (5) ◽  
pp. 2121-2130 ◽  
Author(s):  
Latifa Bouhdoud ◽  
Patricia Villain ◽  
Abderrazzak Merzouki ◽  
Maximilian Arella ◽  
Clément Couture
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Ctl Response ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection triggers a cytotoxic T-lymphocyte (CTL) response mediated by CD8+ and perhaps CD4+ CTLs. The mechanisms by which HIV-1 escapes from this CTL response are only beginning to be understood. However, it is already clear that the extreme genetic variability of the virus is a major contributing factor. Because of the well-known ability of altered peptide ligands (APL) to induce a T-cell receptor (TCR)-mediated anergic state in CD4+ helper T cells, we investigated the effects of HIV-1 sequence variations on the proliferation and cytotoxic activation of a human CD4+ CTL clone (Een217) specific for an epitope composed of amino acids 410 to 429 of HIV-1 gp120. We report that a natural variant of this epitope induced a functional anergic state rendering the T cells unable to respond to their antigenic ligand and preventing the proliferation and cytotoxic activation normally induced by the original antigenic peptide. Furthermore, the stimulation of Een217 cells with this APL generated altered TCR-proximal signaling events that have been associated with the induction of T-cell anergy in CD4+ T cells. Importantly, the APL-induced anergic state of the Een217 T cells could be prevented by the addition of interleukin 2, which restored their ability to respond to their nominal antigen. Our data therefore suggest that HIV-1 variants can induce a state of anergy in HIV-specific CD4+ CTLs. Such a mechanism may allow a viral variant to not only escape the CTL response but also facilitate the persistence of other viral strains that may otherwise be recognized and eliminated by HIV-specific CTLs.

Isolation and Characterization of Human Antigen-Specific TCRαβ+ CD4−CD8− Double Negative Regulatory T Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3306-3306
Author(s):  
Karin Fischer ◽  
Simon Voelkl ◽  
Grzegorz K. Przybylski ◽  
Christian A. Schmidt ◽  
Reinhard Andreesen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Proliferative Response ◽  
Cell Subset ◽  
Cell Receptor ◽  
Treg Cells ◽  
Double Negative ◽  
Isolation And Characterization

Abstract Compelling evidence indicate that regulatory T (Treg) cells play an important role in the maintenance of immune tolerance to self and foreign antigens (Ag). Various subsets of T lymphocytes have been isolated in mice and humans that have the ability to down-regulate the proliferation of autoimmune effector cells. Recently, a novel subset of Ag-specific T-cell receptor (TCR)αβ+ CD4−CD8− (double negative, DN) Treg cells has been found to be able to prevent the rejection of skin and heart allografts by specifically inhibiting the function of anti-graft-specific CD8+ T cells. Here we demonstrate that peripheral DN Treg cells are present in humans, where they constitute about 1% of total CD3+ T cells, and consist of both naïve and Ag-experienced cells. Furthermore, analysis of T-cell receptor excision circles (TRECs) indicate that DN T cells are not recent thymic emigrants, but rather an expanded T-cell subset. MHC multimer staining revelaed a distinct population of DN T cells recognizing common MHC class I-restricted CMV and EBV antigens. DN T cells exhibited a strong proliferative response upon stimulation with allogeneic antigen presenting cells (APC) and secreted high amounts of IFN-γ but no IL-2, with some IL-5, and marginal levels of IL-4 and IL-10. Similar to murine DN Treg cells, human DN Treg cells are able to acquire peptide-HLA-A2 complexes from APCs by cell contact-dependent mechanisms. Furthermore, such acquired peptide-HLA complexes appear to be functionally active, in that CD8+ T cells specific for the HLA-A2-restricted self peptide, Melan-A, became sensitive to apoptosis by neighboring DN T cells after acquisition of Melan-A-HLA-A2 complexes and revealed a reduced proliferative response. These results demonstrate for the first time that a sizeable population of peripheral DN Treg cells exists in humans that are able to suppress Ag-specific T cells. DN Treg cells may serve to limit clonal expansion of allo-Ag-specific T cells after transplantation.

scholarly journals Random T-Cell Receptor Recruitment in Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells from Genetically Identical Twins Infected with the Same HIV-1 Strain

2007 ◽  
Vol 81 (22) ◽  
pp. 12666-12669 ◽  
Author(s):  
Xu G. Yu ◽  
Mathias Lichterfeld ◽  
Katie L. Williams ◽  
Javier Martinez-Picado ◽  
Bruce D. Walker
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Receptor ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte escape mutations represent both a major reason for loss of HIV immune control and a considerable challenge for HIV-1 vaccine design. Previous data suggest that initial HIV-1-specific CD8+ T-cell responses are determined largely by viral and host genetics, but the mechanisms influencing the subsequent viral evolution are unclear. Here, we show a random recruitment of T-cell receptor (TCR) alpha and beta clonotypes of the initial HIV-1-specific CD8+ T cells during primary infection in two genetically identical twins infected simultaneously with the same virus, suggesting that stochastic TCR recruitment of HIV-1-specific CD8+ T cells contributes to the diverse and unpredictable HIV-1 sequence evolution.

scholarly journals Antiretroviral Therapy Restores Diversity in the T-Cell Receptor Vβ Repertoire of CD4 T-Cell Subpopulations among Human Immunodeficiency Virus Type 1-Infected Children and Adolescents

2009 ◽  
Vol 16 (9) ◽  
pp. 1293-1301 ◽  
Author(s):  
Li Yin ◽  
Zhong Chen Kou ◽  
Carina Rodriguez ◽  
Wei Hou ◽  
Maureen M. Goodenow ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Cd4 T Cell ◽  
Cdr3 Length ◽  
Immunodeficiency Virus ◽  
The Impact

ABSTRACT Human immunodeficiency virus (HIV) type 1 infection perturbs the T-cell receptor (TCR) Vβ repertoire. The TCR CDR3 length diversity of individual Vβ families was examined within CD45RA and CD45RO CD4 T cells to assess the impact of the virus on clonality throughout CD4 T-cell activation and differentiation. A cross-sectional and longitudinal cohort study of 13 HIV-infected and 8 age-matched healthy children and adolescents examined the Vβ CDR3 length profiles within CD4 T-cell subsets by the use of spectratyping. HIV-infected subjects demonstrated higher numbers of perturbations in CD4 CD45RA T cells (5.8 ± 4.9 Vβ families) than healthy individuals (1.6 ± 1.8 Vβ families) (P = 0.04). Surprisingly, CD4 CD45RO central memory T cells from infected subjects showed no increased perturbations compared to the perturbations for the same cells from healthy subjects (2.9 ± 3.1 and 1.1 ± 1.8 Vβ families, respectively; P = 0.11). CD4 CD45RA TCR perturbations were higher among infected subjects with >25% CD4 cells than healthy subjects (mean number of perturbed Vβ families, 6.6 ± 5.4; P = 0.04). No correlations between perturbations in CD4 subsets and pretherapy age or viral load were evident. In contrast to CD8 T cells, HIV induces TCR disruptions within CD45RA but not CD45RO CD4 T cells. Therapy-induced viral suppression resulted in increases in thymic output and the normalization of the diversity of TCR within CD45RA CD4 T cells after 2 months of treatment. Perturbations occur prior to CD4 T-cell attrition and normalize with effective antiretroviral therapy. The impact of HIV on the diversity of TCR within naïve, central memory, and effector memory CD4 T cells is distinctly different from that in CD8 T cells.

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