Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues
R. Pat Bucy, … , Ronald T. Mitsuyasu, J. Michael Kilby
R. Pat Bucy, … , Ronald T. Mitsuyasu, J. Michael Kilby
Published May 15, 1999
Citation Information: J Clin Invest. 1999;103(10):1391-1398. https://doi.org/10.1172/JCI5863.
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Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues

Abstract

Previous studies proposed a dynamic, steady-state relationship between HIV-mediated cell killing and T-cell proliferation, whereby highly active antiretroviral therapy (HAART) blocks viral replication and tips the balance toward CD4+ cell repopulation. In this report, we have analyzed blood and lymph node tissues obtained concurrently from HIV-infected patients before and after initiation of HAART. Activated T cells were significantly more frequent in lymph node tissue compared with blood at both time points. Ten weeks after HAART, the absolute number of lymphocytes per excised lymph node decreased, whereas the number of lymphocytes in the blood tended to increase. The relative proportions of lymphoid subsets were not significantly changed in tissue or blood by HAART. The expression levels of mRNA for several proinflammatory cytokines (IFN-γ, IL-1β, IL-6, and macrophage inflammatory protein-1α) were lower after HAART. After therapy, the expression of VCAM-1 and ICAM-1 — adhesion molecules known to mediate lymphocyte sequestration in lymphoid tissue — was also dramatically reduced. These data provide evidence suggesting that initial increases in blood CD4+ cell counts on HAART are due to redistribution and that this redistribution is mediated by resolution of the immune activation that had sequestered T cells within lymphoid tissues.

Authors

R. Pat Bucy, Richard D. Hockett, Cynthia A. Derdeyn, Michael S. Saag, Kathleen Squires, Michael Sillers, Ronald T. Mitsuyasu, J. Michael Kilby

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Figure 1

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Absolute numbers of lymphocytes in blood and a single excision lymph nod...
Absolute numbers of lymphocytes in blood and a single excision lymph node biopsy from level 3 or 4 in the posterior cervical chain before induction of HAART and 10 weeks after HAART in 7 subjects. Blood and lymph node biopsies were obtained on the same day. Different symbols represent individual subjects. Biopsies after HAART were taken from the opposite side of the neck in the same anatomical location as the prior biopsy. The decrease in number of lymphocytes per lymph node is significant (P < 0.05) by paired t test (median: 121 × 106 cells before HAART and 14.4 × 106 cells after HAART). The gross size of the measured lymph node specimens was also significantly decreased (P < 0.05), as determined by paired t test (median: 1.3 cm3 before HAART and 0.5 cm3 after HAART). The increase in lymphocytes in the blood does not reach formal statistical significance (P = 0.11; median: 989 cells/μL before HAART and 1,480 cells/μL after HAART). Note that subject 2 (filled circle; see Table 2), with the highest lymphocyte count and lowest viral load before HAART, showed decreased blood T cells but increased cells in lymph node. This subject confounds the general trend of increased cells in blood but is consistent with an inverse relationship between blood and tissue cells.