Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function

Luciléia Teixeira, Hernan Valdez, Joseph M. McCune, Richard A. Koup, Andrew David Badley, Marc K. Hellerstein, Laura A. Napolitano, Daniel C. Douek, Georgina Mbisa, Steven Deeks, Jeffrey M. Harris, Jason D. Barbour, Barry H. Gross, Isaac R. Francis, Robert Halvorsen, Robert Asaad, Michael M. Lederman

Research output: Contribution to journalArticle

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Abstract

Objective: To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART). Methods: Cross-sectional study of patients with CD4 T cell rises of ≥200×106 cells/ I (CD4 responders; n=10) or <100×106 cells/I (poor responders; n=12) in the first year of therapy. Results: Poor responders were older than CD4 responders (46 versus 38 years; P<0.01) and, before HAART, had higher CD4 cell counts (170 versus 35×106 cells/ I; P=0.11) and CD8 cell counts (780 versus 536×106 cells/I; P=0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44×106 cells/I; P=0.001) and naive phenotype CD8 cells (487 versus 174×106 cells/I; P=0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P=0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5×106 cells/I; P=0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P=0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics. Conclusion: Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.

Original languageEnglish (US)
Pages (from-to)1749-1756
Number of pages8
JournalAIDS
Volume15
Issue number14
DOIs
StatePublished - Sep 28 2001
Externally publishedYes

Fingerprint

HIV-1
T-Lymphocytes
Highly Active Antiretroviral Therapy
T-Cell Antigen Receptor
Phenotype
Telomere
CD4 Lymphocyte Count
Cell Count
Cross-Sectional Studies
Lymphocytes
Glucose
Therapeutics

Keywords

  • AIDS
  • CD4
  • HAART
  • Highly active antiretroviral therapy
  • T cell reconstitution
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Teixeira, L., Valdez, H., McCune, J. M., Koup, R. A., Badley, A. D., Hellerstein, M. K., ... Lederman, M. M. (2001). Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. AIDS, 15(14), 1749-1756. https://doi.org/10.1097/00002030-200109280-00002

Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. / Teixeira, Luciléia; Valdez, Hernan; McCune, Joseph M.; Koup, Richard A.; Badley, Andrew David; Hellerstein, Marc K.; Napolitano, Laura A.; Douek, Daniel C.; Mbisa, Georgina; Deeks, Steven; Harris, Jeffrey M.; Barbour, Jason D.; Gross, Barry H.; Francis, Isaac R.; Halvorsen, Robert; Asaad, Robert; Lederman, Michael M.

In: AIDS, Vol. 15, No. 14, 28.09.2001, p. 1749-1756.

Research output: Contribution to journalArticle

Teixeira, L, Valdez, H, McCune, JM, Koup, RA, Badley, AD, Hellerstein, MK, Napolitano, LA, Douek, DC, Mbisa, G, Deeks, S, Harris, JM, Barbour, JD, Gross, BH, Francis, IR, Halvorsen, R, Asaad, R & Lederman, MM 2001, 'Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function', AIDS, vol. 15, no. 14, pp. 1749-1756. https://doi.org/10.1097/00002030-200109280-00002
Teixeira, Luciléia ; Valdez, Hernan ; McCune, Joseph M. ; Koup, Richard A. ; Badley, Andrew David ; Hellerstein, Marc K. ; Napolitano, Laura A. ; Douek, Daniel C. ; Mbisa, Georgina ; Deeks, Steven ; Harris, Jeffrey M. ; Barbour, Jason D. ; Gross, Barry H. ; Francis, Isaac R. ; Halvorsen, Robert ; Asaad, Robert ; Lederman, Michael M. / Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. In: AIDS. 2001 ; Vol. 15, No. 14. pp. 1749-1756.
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AU - Teixeira, Luciléia

AU - Valdez, Hernan

AU - McCune, Joseph M.

AU - Koup, Richard A.

AU - Badley, Andrew David

AU - Hellerstein, Marc K.

AU - Napolitano, Laura A.

AU - Douek, Daniel C.

AU - Mbisa, Georgina

AU - Deeks, Steven

AU - Harris, Jeffrey M.

AU - Barbour, Jason D.

AU - Gross, Barry H.

AU - Francis, Isaac R.

AU - Halvorsen, Robert

AU - Asaad, Robert

AU - Lederman, Michael M.

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N2 - Objective: To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART). Methods: Cross-sectional study of patients with CD4 T cell rises of ≥200×106 cells/ I (CD4 responders; n=10) or <100×106 cells/I (poor responders; n=12) in the first year of therapy. Results: Poor responders were older than CD4 responders (46 versus 38 years; P<0.01) and, before HAART, had higher CD4 cell counts (170 versus 35×106 cells/ I; P=0.11) and CD8 cell counts (780 versus 536×106 cells/I; P=0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44×106 cells/I; P=0.001) and naive phenotype CD8 cells (487 versus 174×106 cells/I; P=0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P=0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5×106 cells/I; P=0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P=0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics. Conclusion: Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.

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