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Functional γδ T-lymphocyte Defect Associated with Human Immunodeficiency Virus Infections

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Abstract

Background

Antiviral cellular immune responses may influence immunological homeostasis in HIV-infected persons. Recent data indicate that Vγ9/Vδ2 T lymphocytes display potent cytotoxic activities against human cells infected with certain viruses including HIV. Understanding the role of γδ T cells in the course of HIV infection may be helpful for designing novel treatment strategies for HIV-associated disorders.

Materials and Methods

The constitutive recognition of Daudi cells and monoethyl pyrophosphate (Etpp) by peripheral blood Vγ9/Vδ2 T cells was assessed using a proliferation assay. The cytotoxicity of Daudi-stimulated lymphocyte populations was measured by chromium release assays. The HIV infectivity for γδ T cell clones was determined by measuring the levels of HTV p24 in cell supernatants. The effect of in vitro HIV-infection on cytokine mRNA production by γδ T cell clones was assessed by PCR.

Results

The constitutive proliferative responses of peripheral blood Vγ9/Vδ2 T cells and the lytic functions of Daudi-expanded lymphoid cells from HTV+ persons were substantially diminished in comparison with those of HlV-seronegative persons. These alterations were present in asymptomatic HIV+ persons prior to substantial αβ CD4+ T cell loss. Productive fflV infection of γδ T cells in vitro had no measurable effect either on their proliferative response to Daudi stimuli or on the expression of cytokine mRNAs for IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-13.

Conclusions

The constitutive responsiveness of Vγ9/Vδ2 T lymphocytes to Daudi and Etpp is severely altered in HIV+ persons. HTV infection of γδ T cells in vitro does not substantially change their cytokine expression or antigenic response.

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Acknowledgments

We thank Drs. Franklin M. Graziano, and H. Goldstein for their help in obtaining human blood samples, Dr. M. Merle Elloso for helpful discussion, and Ms. K. Elmer for assistance with flow cytometry. This work was supported by grants from the NIH and the Tracy, Jamie and Dawn Ruhrup Memorial Virus Research Fund. This is publication no. 36–052 of WRPRC.

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, 1300 University Ave., Madison, WI, 53706, USA

    Marianne Wallace, Alexander M. Scharko & Miroslav Malkovsky

  2. Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, Wisconsin, USA

    Alexander M. Scharko & C. David Pauza

  3. Department of Human Oncology, University of Wisconsin Medical School, Madison, Wisconsin, USA

    Paul Fisch & Miroslav Malkovsky

  4. Immunology and Virology Research Group, Wisconsin Regional Primate Research Center, Madison, Wisconsin, USA

    C. David Pauza & Miroslav Malkovsky

  5. Department of Medicine I, University Hospital Freiburg, Freiburg, Germany

    Paul Fisch

  6. Department of Oral Biology, University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA

    Koichi Imaoka, Shigetada Kawabata, Kohtaro Fujihashi & Hiroshi Kiyono

  7. Howard Hughes Medical Institute and Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA

    Yoshimasa Tanaka & Barry R. Bloom

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  1. Marianne Wallace
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Wallace, M., Scharko, A.M., Pauza, C.D. et al. Functional γδ T-lymphocyte Defect Associated with Human Immunodeficiency Virus Infections. Mol Med 3, 60–71 (1997). https://doi.org/10.1007/BF03401668

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