Functional gamma delta T-lymphocyte defect associated with human immunodeficiency virus infections.
BACKGROUND
Antiviral cellular immune responses may influence immunological homeostasis in HIV-infected persons. Recent data indicate that V gamma 9/V delta 2 T lymphocytes display potent cytotoxic activities against human cells infected with certain viruses including HIV. Understanding the role of gamma delta T cells in the course of HIV infection may be helpful for designing novel treatment strategies for HIV-associated disorders.


METHODS
The constitutive recognition of Daudi cells and monoethyl pyrophosphate (Etpp) by peripheral blood V gamma 9/V delta 2 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 gamma delta T cell clones was determined by measuring the levels of HIV p24 in cell supernatants. The effect of in vitro HIV-infection on cytokine mRNA production by gamma delta T cell clones was assessed by PCR.


RESULTS
The constitutive proliferative responses of peripheral blood V gamma 9/V delta 2 T cells and the lytic functions of Daudi-expanded lymphoid cells from HIV+ persons were substantially diminished in comparison with those of HIV-seronegative persons. These alterations were present in asymptomatic HIV+ persons prior to substantial alpha beta CD4+ T cell loss. Productive HIV infection of gamma delta 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-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-13.


CONCLUSIONS
The constitutive responsiveness of V gamma 9/V delta 2 T lymphocytes to Daudi and Etpp is severely altered in HIV+ persons. HIV infection of gamma delta T cells in vitro does not substantially change their cytokine expression or antigenic response.
Wallace
M
M
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison 53706, USA.
Scharko
A M
AM
Pauza
C D
CD
Fisch
P
P
Imaoka
K
K
Kawabata
S
S
Fujihashi
K
K
Kiyono
H
H
Tanaka
Y
Y
Bloom
B R
BR
Malkovsky
M
M
D002455:Cell Division; D002999:Clone Cells; D016207:Cytokines / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D016655:HIV Core Protein p24; D016692:Receptors, Antigen, T-Cell, gamma-delta