Supranormal thymic output up to 2 decades after HIV-1 infection. (13th March 2016)

• Record Type: Journal Article
• Authors: Aguilera-Sandoval, Christian R.; Yang, Otto O.; Jojic, Nebojsa; Lovato, Pietro; Chen, Diana Y.; Boechat, Maria Ines; Cooper, Paige; Zuo, Jun; Ramirez, Christina; Belzer, Marvin; Church, Joseph A.; Krogstad, Paul
• Is Part Of: AIDS. Volume 30:Number 5(2016)
• Publication Date: 2016-03-13
• Subjects: adolescents -- CD4+ T cells -- immune reconstitution -- perinatal HIV infection -- recent thymic emigrant -- T-cell receptor -- thymopoiesis -- T-cell receptor recombination excision circles; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001010
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objectives: AIDS is caused by CD4 + T-cell depletion. Although combination antiretroviral therapy can restore blood T-cell numbers, the clonal diversity of the reconstituting cells, critical for immunocompetence, is not well defined. Methods: We performed an extensive analysis of parameters of thymic function in perinatally HIV-1-infected ( n = 39) and control ( n = 28) participants ranging from 13 to 23 years of age. CD4 + T cells including naive (CD27 + CD45RA + ) and recent thymic emigrant (RTE) (CD31 + /CD45RA + ) cells, were quantified by flow cytometry. Deep sequencing was used to examine T-cell receptor (TCR) sequence diversity in sorted RTE CD4 + T cells. Results: Infected participants had reduced CD4 + T-cell levels with predominant depletion of the memory subset and preservation of naive cells. RTE CD4 + T-cell levels were normal in most infected individuals, and enhanced thymopoiesis was indicated by higher proportions of CD4 + T cells containing TCR recombination excision circles. Memory CD4 + T-cell depletion was highly associated with CD8 + T-cell activation in HIV-1-infected persons and plasma interlekin-7 levels were correlated with naive CD4 + T cells, suggesting activation-driven loss and compensatory enhancement of thymopoiesis. Deep sequencing of CD4 + T-cell receptor sequences in well compensated infected persons demonstrated supranormal diversity, providing additional evidence of enhanced thymic output. Conclusion: Despite up to two decades of infection, many individuals have remarkable thymic reserve to compensate for ongoing CD4 + T-cell loss, although there is ongoing viral replication and immune activation despite combination antiretroviral therapy. The longer term sustainability of this physiology remains to be determined. Abstract : Supplemental Digital Content is available in the text