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

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. I...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HIV T follicular helper cells germinal centers interferon reconstitution Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/0ae51d691b0641559c9ba2d6466a68a7
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spelling	oai:doaj.org-article:0ae51d691b0641559c9ba2d6466a68a72021-12-02T00:00:50ZRapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease1664-322410.3389/fimmu.2021.752782https://doaj.org/article/0ae51d691b0641559c9ba2d6466a68a72021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.752782/fullhttps://doaj.org/toc/1664-3224Low 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.Chun-Shu WongClarisa M. BucknerSilvia Lucena LageLuxin PeiFelipe L. AssisEric W. DahlstromSarah L. AnzickKimmo VirtanevaAdam RupertJeremy L. DavisTing ZhouElizabeth LaidlawMaura ManionFrances GalindoMegan AndersonCatherine A. SeamonMichael C. SnellerAndrea LiscoClaire DeleageStefania PittalugaSusan MoirIrini SeretiFrontiers Media S.A.articleHIVT follicular helper cellsgerminal centersinterferonreconstitutionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV T follicular helper cells germinal centers interferon reconstitution Immunologic diseases. Allergy RC581-607
spellingShingle	HIV T follicular helper cells germinal centers interferon reconstitution Immunologic diseases. Allergy RC581-607 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 Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
description	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.
format	article
author	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
author_facet	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
author_sort	Chun-Shu Wong
title	Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
title_short	Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
title_full	Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
title_fullStr	Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
title_full_unstemmed	Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease
title_sort	rapid emergence of t follicular helper and germinal center b cells following antiretroviral therapy in advanced hiv disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0ae51d691b0641559c9ba2d6466a68a7
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Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease

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