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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Analysis of TCR Vβ repertoire diversity by spectratype analysis of TCR V...
Analysis of TCR Vβ repertoire diversity by spectratype analysis of TCR Vβ CDR3 length. Shown is analysis for 16 TCR Vβ families. (a and b) Analysis beginning before (week 3; a) and after (week 47; b) HAART-associated CD4+ T-cell rises in PB T cells. (c) Same analysis at week 47 in purified CD4+ T cells. Because of the recombination process of TCRs during T-cell development, TCR Vβ CDR3 sizes vary by as many as eight amino acids between any two TCR chains. This method of TCR repertoire analysis combines RT-PCR technology with analysis of message size in acrylamide gels to determine the relative abundance of TCR transcripts bearing particular CDR3 sizes within a T-cell sample. Thus, more normal or polyclonal patterns of TCR usage are seen in d in the study of a normal control. Less normal or oligoclonal patterns are seen in a for Vβ3 and Vβ6 T cells. Our analysis showed in patient no. 9 that TCR usage did not change in most Vβ families over time. However, rare new or enhanced usage of TCR clones was documented by week 47 in several Vβ families that were compatible with T-cell responses to antigenic challenge peripherally over time. c shows that the TCR clone patterns seen in unfractionated PB T cells at week 47 were also similar to the patterns seen in purified CD4+ T cells assayed from the same time point. (d) For comparison, TCR repertoire analysis in a representative normal non–HIV-1–infected subject is shown; it demonstrates the normal spectrum of TCR CDR3 length analysis. CDR3, complementary determining region-3; RT, reverse transcriptase; TCR, T-cell receptor; Vβ, β-chain variable region.