Function of the Thymus in HIV-Infected Adults

Poulin, Jean-François; Sékaly, Rafick‐Pierre

doi:10.1001/jama.282.3.219

Cited by 12 publications

(2 citation statements)

References 7 publications

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“…The recovery of T cell numbers during highly active antiretroviral therapy (HAART) 3 can occur through a number of different mechanisms, which may result in the reconstitution of qualitatively different immune function. Peripheral expansion or redistribution of pre-existing T cells (17)(18)(19)(20)22) will result in a T cell repertoire that reflects that already marred by HIV infection, whereas de novo generation of new naive T cells from the thymus (23)(24)(25)(26)(27) will reconstitute a more diverse T cell repertoire (28,29).…”

Section: T Cell Depletion Of Cd4mentioning

confidence: 99%

Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection

Douek

Betts

Hill

et al. 2001

The Journal of Immunology

233

199

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The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO−CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS.

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Section: T Cell Depletion Of Cd4mentioning

confidence: 99%

Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection

Douek

Betts

Hill

et al. 2001

The Journal of Immunology

233

199

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“…2,3 Furthermore, the adult thymus can contribute to immune reconstitution in individuals following antiretroviral therapy, 2,14,15 and following myeloablative chemotherapy and autologous hematopoietic stem cell transplantation. 16 T cells generated de novo from thymopoiesis have a broad TCR repertoire and are theoretically more capable of responding to neoantigens effectively.…”

Section: Introductionmentioning

confidence: 99%

Effects of exogenous interleukin-7 on human thymus function

Okamoto

Douek

McFarland

et al. 2002

Blood

125

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Immune reconstitution is a critical component of recovery after treatment of human immunodeficiency virus (HIV) infection, cancer chemotherapy, and hematopoietic stem cell transplantation. The ability to enhance T-cell production would benefit such treatment. We examined the effects of exogenous interleukin-7 (IL-7) on apoptosis, proliferation, and the generation of T-cell receptor rearrangement excision circles (TRECs) in human thymus. Quantitative polymerase chain reaction demonstrated that the highest level of TRECs (14 692 copies/10 000 cells) was present in the CD1a ؉ CD3 ؊ CD4 ؉ CD8 ؉ stage in native thymus, suggesting that TREC generation occurred following the cellular division in this subpopulation. In a thymic organ culture system, exogenous IL-7 increased the TREC frequency in fetal as well as infant thymus, indicating increased T-cell receptor (TCR) rearrangement. Although this increase could be due to the effect of IL-7 to increase thymocyte proliferation and decrease apoptosis of immature CD3 ؊ cells, the in vivo experiments using NOD/LtSz-scid mice given transplants of human fetal thymus and liver suggested that IL-7 can also directly enhance TREC generation. Our results provide compelling evidence that IL-7 has a direct effect on increasing TCR-␣␤ rearrangement and indicate the potential use of IL-7 for enhancing de novo naïve T-cell generation in immunocompromised patients. ( IntroductionIt has been reported that T-cell numbers are maintained in adults predominantly through the expansion of postthymic, memory T cells, whereas in infants, T cells are predominantly maintained through the production of new naïve T cells by the thymus. 1 However, others and we have recently demonstrated that the adult thymus is still capable of thymopoiesis and can contribute to T-cell reconstitution in adults. 2,3 Several methods have been used to measure thymopoietic capacity. Thymic size as measured by radiographic imaging 1 and volumetric computed tomography measurements 4,5 have been correlated with numbers of CD4 ϩ CD45RA ϩ naïve T cells, and the number of phenotypically naïve T cells after transplantation has been shown to correlate with antigen-specific function. 6 However, there are concerns about limitations of estimating thymic function based on naïve T-cell phenotype alone. T cells expressing a naïve phenotype are not necessarily accurate surrogate markers of thymic function. Following thymic emigration, CD45RA ϩ naïve T cells can have a long quiescent life span, 7 may proliferate in an antigen-independent manner, 8 or may rapidly convert to CD45RO ϩ memory/effector phenotype T cells. 9 Furthermore, naïve T-cell markers may be acquired by memory T cells (especially CD8 ϩ T cells), 9,10 further compounding the difficulty in accurately enumerating naïve T cells. 11,12 To measure thymic function more directly in humans, we recently described an assay that quantifies an episomal DNA by-product of the T-cell receptor (TCR) rearrangement process. 2 These TCR rearrangement excision circles (TRECs) contain the ...

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Thymic Function

Dutrieux¹,

Cheynier²

2014

Encyclopedia of AIDS

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Function of the Thymus in HIV-Infected Adults

Cited by 12 publications

References 7 publications

Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection

Evidence for Increased T Cell Turnover and Decreased Thymic Output in HIV Infection

Effects of exogenous interleukin-7 on human thymus function

Thymic Function

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