TY - JOUR
T1 - Multiparameter evaluation of human thymic function
T2 - Interpretations and caveats
AU - Harris, Jeffrey M.
AU - Hazenberg, Mette D.
AU - Poulin, Jean François
AU - Higuera-Alhino, Dana
AU - Schmidt, Diane
AU - Gotway, Michael
AU - McCune, Joseph M.
N1 - Funding Information:
The authors would like to thank Valerie Stepps and Marty Bigos for their expertise in flow cytometry and cell sorting, Mary Beth Hanley for her assistance with assays and sample management, Bob Grant for statistical advice, and Morgan Jenkins, Krishna Komanduri, Elizabeth Sinclair, and Laura Napolitano for thoughtful discussions. This work was supported by grants from the National Institute of Health (NIH) to J.M. McCune (R01 AI43864 and R37 40312) and to J.M. Harris (K23 AI050435), and from the European Molecular Biology Organization (EMBO) to M.D. Hazenberg (ALTF 254-2002). J.M.M. is an Elizabeth Glaser Pediatric AIDS Foundation Scientist and a recipient of the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.
PY - 2005/5
Y1 - 2005/5
N2 - After the provision of highly active antiretroviral therapy (HAART), the level of circulating CD4+ T cells increases in many adults infected with the human immunodeficiency virus, type 1 (HIV). To study factors involved in immune reconstitution, we have measured thymic abundance by CT scans, circulating naive-phenotype CD4+ T cells by flow cytometry, and T cell receptor (TCR) rearrangement excision circles (TRECs) by quantitative PCR in 40 virologically suppressed, HIV-infected adults and 33 age-matched, HIV-uninfected controls. In HIV-uninfected subjects, naive T cell numbers, thymic abundance, and the frequency of circulating naive CD4+ T cells bearing TRECs decreased with age, as expected. When corrected for this relationship with age, naive T cell numbers correlated significantly with naive T cell TREC frequencies. Virologically suppressed HIV-infected subjects had higher TREC frequencies, and subjects over the age of 39 were more likely to have abundant thymus compared to age-matched, HIV-uninfected adults. Nevertheless, all HIV-infected subjects had reduced absolute numbers of naive T cells, irrespective of thymic size, age, or TREC frequencies. These data illustrate the complex relationship between these measures of thymic size and function and underscore the need to develop more definitive measures of thymic function in the future.
AB - After the provision of highly active antiretroviral therapy (HAART), the level of circulating CD4+ T cells increases in many adults infected with the human immunodeficiency virus, type 1 (HIV). To study factors involved in immune reconstitution, we have measured thymic abundance by CT scans, circulating naive-phenotype CD4+ T cells by flow cytometry, and T cell receptor (TCR) rearrangement excision circles (TRECs) by quantitative PCR in 40 virologically suppressed, HIV-infected adults and 33 age-matched, HIV-uninfected controls. In HIV-uninfected subjects, naive T cell numbers, thymic abundance, and the frequency of circulating naive CD4+ T cells bearing TRECs decreased with age, as expected. When corrected for this relationship with age, naive T cell numbers correlated significantly with naive T cell TREC frequencies. Virologically suppressed HIV-infected subjects had higher TREC frequencies, and subjects over the age of 39 were more likely to have abundant thymus compared to age-matched, HIV-uninfected adults. Nevertheless, all HIV-infected subjects had reduced absolute numbers of naive T cells, irrespective of thymic size, age, or TREC frequencies. These data illustrate the complex relationship between these measures of thymic size and function and underscore the need to develop more definitive measures of thymic function in the future.
KW - AIDS
KW - Chronic HIV infection
KW - Human
KW - Immune reconstitution
KW - Naive T lymphocyte
KW - Recent thymic emigrants
KW - TREC
KW - Thymic function
KW - Thymus
UR - http://www.scopus.com/inward/record.url?scp=18844456552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18844456552&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2004.12.008
DO - 10.1016/j.clim.2004.12.008
M3 - Article
C2 - 15885636
AN - SCOPUS:18844456552
SN - 1521-6616
VL - 115
SP - 138
EP - 146
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2
ER -