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.
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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Journal of virology | 2000 |
Effect of Highly Active Antiretroviral Therapy and Thymic Transplantation on Immunoreconstitution in HIV Infection
M. Louise Markert, Charles B. Hicks, John A. Bartlett, J. Les Harmon, Laura P. Hale, Michael L. Greenberg, Guido Ferrari, Janet Ottinger, Andreas Boeck, Amy L. Kloster, Tanya M. M, Laughlin, Karen B. Bleich, Ross M. Ungerleider, H. Kim Lyerly, William E. Wilkinson, Franck S. Rousseau, M Argo E. Heath-Chiozzi, John M. Leonard, Ashley T. Haase, George M ., R. Pat Bucy, Daniel C. Douek, Richard A. Koup, Barton F. Haynes, Dani P. Bolognesi, Kent J. Weinhold |
AIDS Research and Human Retroviruses | 2000 |
Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue
AS Protheroe, C Pickard, PW Johnson, T Craddock, J Shefta, K Short, F Lancaster, PJ Selby, J Henwood, AW Boylston |
British Journal of Haematology | 2000 |
The Role of the Thymus in Immune Reconstitution in Aging, Bone Marrow Transplantation, and HIV-1 Infection
BF Haynes, ML Markert, GD Sempowski, DD Patel, LP Hale |
Annual Review of Immunology | 2000 |
Stimulation of Thymocyte Proliferation by Phosphorothioate DNA Oligonucleotides
RB Mannon, C Nataraj, DS Pisetsky |
Cellular Immunology | 2000 |
A case???control study of virological and immunological effects of highly active antiretroviral therapy in HIV-infected patients with advanced age
R Manfredi, F Chiodo |
AIDS | 2000 |
CHANGES IN IMMUNE FUNCTION WITH AGE
RL Yung |
Rheumatic Disease Clinics of North America | 2000 |
Detection of T cell receptor circles (TRECs) as biomarkers for de novo T cell synthesis using a quantitative polymerase chain reaction–enzyme linked immunosorbent assay (PCR–ELISA)
L Al-Harthi, G Marchetti, CM Steffens, JF Poulin, RP Sékaly, A Landay |
Journal of Immunological Methods | 2000 |
Hematopoietic Stem Cells in HIV Disease
DT Scadden, H Shen, T Cheng |
JNCI Monographs | 2000 |
Linkage of the CCR5Δ32 Mutation with a Functional Polymorphism of CD45RA
HX Liao, DC Montefiori, DD Patel, DM Lee, WK Scott, M Pericak-Vance, BF Haynes |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Diversity of Human αβ T Cell Receptors
C Keşmir, JA Borghans, RJ de Boer |
Science | 2000 |
Analysis of the human thymic perivascular space during aging
KG Flores, J Li, GD Sempowski, BF Haynes, LP Hale |
Journal of Clinical Investigation | 1999 |
Normal Telomere Lengths in Naive and Memory CD4+ T Cells in HIV Type 1 Infection: A Mathematical Interpretation
KC Wolthers, AJ Noest, SA Otto, F Miedema, RJ de Boer |
AIDS Research and Human Retroviruses | 1999 |
Immune reconstitution in lymphoid tissue following potent antiretroviral therapy
J Andersson, TE Fehniger |
Clinical Immunology Newsletter | 1999 |
The human thymus: A new perspective on thymic function, aging, and hiv infection
CM Steffens, G Marchetti, A Landay, L Al-Harthi |
Clinical Immunology Newsletter | 1999 |
HIV infection: where have all the T cells gone?
S Rowland-Jones |
The Lancet | 1999 |
Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy
L Zhang, SR Lewin, M Markowitz, HH Lin, E Skulsky, R Karanicolas, Y He, X Jin, S Tuttleton, M Vesanen, H Spiegel, R Kost, J Lunzen, HJ Stellbrink, S Wolinsky, W Borkowsky, P Palumbo, LG Kostrikis, DD Ho |
Journal of Experimental Medicine | 1999 |
Increases in T Cell Telomere Length in HIV Infection after Antiretroviral Combination Therapy for HIV-1 Infection Implicate Distinct Population Dynamics in CD4+ and CD8+ T Cells
S Kaushal, AL Landay, MM Lederman, E Connick, J Spritzler, DR Kuritzkes, H Kessler, BL Levine, DC st. Louis, CH June |
Clinical Immunology | 1999 |
Immune reconstitution in AIDS: oncologic implications and hematologic approaches
DT Scadden |
Current Opinion in Oncology | 1999 |
HIV Infection and the Dynamic Interplay between the Thymus and the Peripheral T Cell Pool
BF Haynes |
Clinical Immunology | 1999 |
Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1-Infected Individuals before and after Effective Therapy
L Zhang, SR Lewin, M Markowitz, HH Lin, E Skulsky, R Karanicolas, Y He, X Jin, S Tuttleton, M Vesanen, H Spiegel, R Kost, J Lunzen, HJ Stellbrink, S Wolinsky, W Borkowsky, P Palumbo, LG Kostrikis, DD Ho |
Journal of Experimental Medicine | 1999 |
Generation of Functional Thymocytes in the Human Adult
BD Jamieson, DC Douek, S Killian, LE Hultin, DD Scripture-Adams, JV Giorgi, D Marelli, RA Koup, JA Zack |
Immunity | 1999 |
The human thymus: A chimeric organ comprised of central and peripheral lymphoid components
BF Haynes, LP Hale |
Immunologic Research | 1998 |