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 1

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Immunohistological analysis of the thymus in HIV infection. (a–d) Thymus...
Immunohistological analysis of the thymus in HIV infection. (a–d) Thymus from HIV-1+ patient no. 1 with no thymopoiesis. (e–h) Thymus from HIV-1+ patient no. 2 with areas of active thymopoiesis. (a) Hematoxylin and eosin stain of patient no. 1's lymphoid thymus. ×13. (b) A similar area as in a, with thymic epithelium in immunohistological analysis reactive with antikeratin antibody (brown central areas). All keratin+ thymic epithelium (e) in the true thymus is collapsed (dark brown areas) and devoid of lymphocytes, with a surrounding infiltrate of blue mononuclear cells present in the thymic perivascular space (P). ×13. (c) Immunohistological stain of CD8+ T cells (brown cells; see arrows for examples) in the perivascular space (P) around a central empty thymic epithelial island (e). The dotted line surrounds thymic true epithelial thymus areas (e), and the short arrow points out a rare CD8+ T cell within the true epithelial thymus (e). ×66. (d) Many of the perivascular space (P) CD8+ cells are reactive with MAB TIA-1 (arrows) and therefore are mature effector cytotoxic T cells. ×66. e–h are from patient no. 2's thymus. ×33. (e) Light microscopic view of patient no. 2's thymus (hematoxylin and eosin stain with a Hassall's body [h] in the thymus medulla). (f) Immunohistological analysis with antikeratin antibody, with areas of normal-appearing keratin+ thymic epithelium (brown areas) filled with lymphocytes (blue areas) intermingled with thymic epithelium (arrows). Most developing thymocytes are CD3+ T cells (arrows in g), many of which are normal CD1a+ cortical thymocytes (brown cells, arrows in h). A subset of these CD1a+, CD3+ immature thymocytes were actively dividing as determined by nuclear reactivity with MAB mib-1 (not shown). MAB, monoclonal antibody.