Multiparameter evaluation of human thymic function: interpretations and caveats.
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.
Harris
Jeffrey M
JM
Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94103, USA.
Hazenberg
Mette D
MD
Poulin
Jean-François
JF
Higuera-Alhino
Dana
D
Schmidt
Diane
D
Gotway
Michael
M
McCune
Joseph M
JM
D000328:Adult; D000367:Age Factors; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D015658:HIV Infections / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D009929:Organ Size; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000276:immunology*; D014057:Tomography, X-Ray Computed