Apoptosis in T-Lymphocyte Subsets in Human Immunodeficiency Virus-Infected Children Measured Immediately Ex Vivo and following In Vitro Activation

Niehues, Tim; McCloskey, Thomas W.; Ndagijimana, Jennifer; Horneff, Gerd; Wahn, V.; Pahwa, Savita

doi:10.1128/cdli.8.1.74-78.2001

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…Another important question is whether particular clones become susceptible to apoptosis. High levels of CD8-cell apoptosis in HIV-infected children have been demonstrated previously (17). This study has demonstrated that the information gathered from qualitative PCR methods and from quantitative FC methods for the analysis of TCR V␤ repertoire is different.…”

Section: Discussionmentioning

confidence: 87%

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

Kharbanda

McCloskey

Pahwa

et al. 2003

Clin Vaccine Immunol

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Perturbations in the T-cell receptor (TCR) V␤ 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 V␤ subfamilies was assessed for an increased or decreased percentage in CD4 and CD8 T cells, and by PCR, 22 TCR V␤ 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 V␤ 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 V␤ families classified with clonal dominance by CDR3 spectratyping, only 18 of these exhibited increased expression by FC. Patients with high numbers of CD8-TCR V␤ families with decreased percentages had reduced percentages of total CD4 T cells. Increases in the number of CD4-TCR V␤ 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 V␤ families at cellular and molecular levels yields different information and that our understanding of the immune response to HIV is still evolving.The majority of peripheral blood CD4 and CD8 T cells express the ␣␤ T-cell receptor (TCR), with the ␤ chain represented by variable segments which are grouped into families based on sequence homology (16). A complete T-cell repertoire is indicative of an intact T-cell population with the potential to recognize a wide range of immunogens. Numerous reports have documented changes in the TCR V␤ repertoire during human immunodeficiency virus (HIV) infection in relation to disease progression and the effect of therapy (4,5,(8)(9)(10)(19)(20)(21)(22)(23). CDR3 length spectratyping (8,19,21) and flow cytometric (FC) analysis of TCR V␤ families labeled with specific monoclonal antibodies (MAbs) (4,7,26) are among the most frequently used assays for the analysis of TCR V␤ repertoire in HIV infection. The CDR3 spectratype is an indicator of the relative proportion of cells in each TCR V␤ family with CDR3 of particular lengths, while labeling of cells with TCR-V␤-specific MAbs provides a quantitative assessment of the percentages of particular TCR V␤ families in T cells. Thus, evaluation of the TCR V␤ repertoire with MAbs, in combination with CDR3 spectratyping, is expected to provide complementary information. In the present study, we analyzed the TCR V␤ repertoire in the CD4 and CD8 T cells of 22 HIV-infected children by CDR3 length analysis and by FC. MATERIALS AND METHODSPatient population. TCR V␤ repertoire analyses by PCR and FC were performed concurrently in 22 HIV-infected c...

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Section: Discussionmentioning

confidence: 87%

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

Kharbanda

McCloskey

Pahwa

et al. 2003

Clin Vaccine Immunol

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“…21 §Laboratory normal values as mean percentage values in parentheses. 22,23 ID. 9 In our case, it appeared to be related to travel and responded appropriately to conventional antibiotic therapy.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor κB essential modulator–deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia

Niehues¹,

Reichenbach²,

Neubert³

et al. 2004

Journal of Allergy and Clinical Immunology

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117

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“…tients with HIV infection and regulatory lymphocytes contribute to immunosuppression [5][6][7][8][9][10][11][12].…”

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confidence: 99%

Antimicrobial-Specific Cell-Mediated Immune Reconstitution in Children with Advanced Human Immunodeficiency Virus Infection Receiving Highly Active Antiretroviral Therapy

Weinberg

Pahwa

Oyomopito³

et al. 2004

Clinical Infectious Diseases

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To identify virological and immunological correlates of microbial-specific immune reconstitution in children with advanced human immunodeficiency virus (HIV) infection, Candida- and tetanus-specific lymphocyte proliferation was measured in 165 children initiating a new highly active antiretroviral therapy (HAART) regimen. During the study, the proportions of children with immunity to Candida and tetanus increased from 53% to 66% and 19% to 22%, respectively. Tetanus immunity was associated with an HIV load < or =400 RNA copies/mL and with Candida immunity. At the end of the study, 23% of the patients with baseline negative lymphocyte proliferation had tetanus immunity, and 65% had Candida immunity. Reconstitution of tetanus immunity correlated with lower end-of-study HIV loads and activated CD8+ cell percentages and higher baseline and in-study CD4+ cell percentages, but not with a gain of CD4+ cells. Reconstitution of Candida immunity showed similar trends. In conclusion, children with advanced HIV infection receiving HAART reconstituted Candida immunity more readily than they did tetanus immunity, suggesting a role for antigen reexposure. Additional factors for immune reconstitution were low HIV load, high CD4+ cell percentages, and low levels of activated CD8+ cells.

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Apoptosis in T-Lymphocyte Subsets in Human Immunodeficiency Virus-Infected Children Measured Immediately Ex Vivo and following In Vitro Activation

Cited by 13 publications

References 23 publications

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

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

Nuclear factor κB essential modulator–deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia

Antimicrobial-Specific Cell-Mediated Immune Reconstitution in Children with Advanced Human Immunodeficiency Virus Infection Receiving Highly Active Antiretroviral Therapy

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