Frontiers in Immunology (Dec 2021)

Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease

  • Chun-Shu Wong,
  • Clarisa M. Buckner,
  • Silvia Lucena Lage,
  • Luxin Pei,
  • Felipe L. Assis,
  • Eric W. Dahlstrom,
  • Sarah L. Anzick,
  • Kimmo Virtaneva,
  • Adam Rupert,
  • Jeremy L. Davis,
  • Ting Zhou,
  • Elizabeth Laidlaw,
  • Maura Manion,
  • Frances Galindo,
  • Megan Anderson,
  • Catherine A. Seamon,
  • Michael C. Sneller,
  • Andrea Lisco,
  • Claire Deleage,
  • Stefania Pittaluga,
  • Susan Moir,
  • Irini Sereti

DOI
https://doi.org/10.3389/fimmu.2021.752782
Journal volume & issue
Vol. 12

Abstract

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Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.

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