Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection
Barton F. Haynes, … , Ashley T. Haase, John A. Bartlett
Barton F. Haynes, … , Ashley T. Haase, John A. Bartlett
Published February 15, 1999
Citation Information: J Clin Invest. 1999;103(4):453-460. https://doi.org/10.1172/JCI5201.
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Article

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection

Abstract

A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we studied the clinical course of HIV-1 infection in three patients thymectomized for myasthenia gravis and determined the effect of antiretroviral therapy on CD4+ T cells. We found that five of seven patients had thymus tissue at autopsy and that all thymuses identified had inflammatory infiltrates surrounding lymphodepleted thymic epithelium. Two of seven patients also had areas of thymopoiesis; one of these patients had peripheral blood CD4+ T-cell levels of <50/mm3 for 51 months prior to death. Of three thymectomized patients, one rapidly progressed to AIDS, one progressed to AIDS over seven years (normal progressor), whereas the third remains asymptomatic at least seven years after seroconversion. Both latter patients had rises in peripheral blood CD4+ T cells after antiretroviral therapy. Most patients who died of complications of HIV-1 infection did not have functional thymus tissue, and when present, thymopoiesis did not prevent prolonged lymphopenia. Thymectomy before HIV-1 infection did not preclude either peripheral CD4+ T-cell rises or clinical responses after antiretroviral therapy.

Authors

Barton F. Haynes, Laura P. Hale, Kent J. Weinhold, Dhavalkumar D. Patel, Hua-Xin Liao, Peter B. Bressler, Dawn M. Jones, James F. Demarest, Kristin Gebhard-Mitchell, Ashley T. Haase, John A. Bartlett

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Figure 3

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HIV-1–expressing cells are present in the thymic perivascular space as w...
HIV-1–expressing cells are present in the thymic perivascular space as well as in the true epithelial thymus. In situ hybridization for HIV-1 mRNA was performed in patient no. 2 in combination with immunohistological analysis for antikeratin antibody reactivity to identify the true thymic epithelial space (keratin+) and the thymic perivascular space (keratin–). There are cells with HIV-1 RNA both in the islands of true thymus with brown-stained keratin+ epithelium (e) as well as in the intervening perivascular space (P). In the developed radioautograph after in situ hybridization with radiolabeled HIV-1–specific probe, cells with HIV-1 RNA that bound probe have overlying collections of silver grains. Epipolarized light reflected from the grains imparts a yellow color to the cells.