Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections

Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4+ cell loss from blood of macaques undergoing an...

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Bibliographic Details
Published in:International immunology 1997-05, Vol.9 (5), p.703-712
Main Authors: Rosenberg, Y J, Cafaro, A, Brennan, T, Greenhouse, J G, Villinger, F, Ansari, A A, Brown, C, McKinnon, K, Bellah, S, Yalley-Ogunro, J, Elkins, W R, Gartner, S, Lewis, M G
Format: Article
Language:English
Subjects:
Acute Disease
AIDS/HIV
Animals
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis
Cytokines - blood
Cytokines - physiology
Disease Susceptibility
Interferon-gamma - blood
Interferon-gamma - genetics
Lymph Nodes - immunology
Lymphopenia - blood
Lymphopenia - immunology
Macaca fascicularis
Macaca mulatta
Macaca nemestrina
Primates
RNA, Messenger - biosynthesis
Simian Acquired Immunodeficiency Syndrome - immunology
simian immunodeficiency virus
Simian Immunodeficiency Virus - immunology
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
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Summary:Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4+ cell loss from blood of macaques undergoing an acute primary SIV infection might be due to increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus. The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4+ cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible. CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged despite lymphocyte loss from blood. Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration. These results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4+ cell depletion throughout infection.
ISSN:0953-8178
1460-2377
1460-2377
DOI:10.1093/intimm/9.5.703