Dysregulation of memory B cells and circulating T follicular helper cells is a predictor of poor immune recovery in HIV-infected patients on antiretroviral therapy

Yan Liu; Zhen Li; Xiaofan Lu; Yi-Qun Kuang; Deshenyue Kong; Xin Zhang; Xiaodong Yang; Xiuwen Wang; Tingting Mu; Hu Wang; Yihang Zhang; Junyan Jin; Wei Xia; Hao Wu; Tong Zhang; Christiane Moog; Bin Su

doi:10.1002/jmv.28559

Dysregulation of memory B cells and circulating T follicular helper cells is a predictor of poor immune recovery in HIV-infected patients on antiretroviral therapy

J Med Virol. 2023 Feb;95(2):e28559. doi: 10.1002/jmv.28559.

Authors

Yan Liu¹, Zhen Li¹, Xiaofan Lu¹, Yi-Qun Kuang^{2

3}, Deshenyue Kong^{2

3}, Xin Zhang¹, Xiaodong Yang¹, Xiuwen Wang¹, Tingting Mu¹, Hu Wang¹, Yihang Zhang¹, Junyan Jin¹, Wei Xia¹, Hao Wu¹, Tong Zhang¹, Christiane Moog⁴, Bin Su¹

Affiliations

¹ Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
² NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.
³ Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China.
⁴ Laboratoire d'ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.

PMID: 36755363
DOI: 10.1002/jmv.28559

Abstract

T follicular helper (Tfh) cells and their interactions with B cells within the germinal center play extensive roles in human immunodeficiency virus (HIV) pathology. However, their association with immune reconstitution during antiretroviral therapy (ART) is still unclear. The aim of this study was to determine the impact of Tfh and memory B cell function on T helper cell recovery in patients with acute or chronic HIV infection. A total of 100 HIV-infected individuals were enrolled in our study, classified into acute and chronic HIV infection groups (60 and 40, respectively), and subsequently classified into immunological responder (IR) and immunological nonresponder (INR) subgroups according to immune recovery outcomes after 96 weeks of ART. Liquid chromatography-mass spectrometry was used to quantify the temporal regulation patterns of B and CD4⁺ T-cell profiles among patients, and flow cytometry was used to investigate certain subsets of B and T cells. Here we showed that the prevalence of Tfh cells in the T helper cell population correlated negatively with CD4⁺ T-cell recovery. The proportion of CXCR3^- Tfh cells in patients with acute or chronic infection was associated with CD4⁺ T-cell count recovery, and the proportion of CD21⁺ memory B cells at baseline was significantly higher in those with improved immune recovery outcomes. Universal proteomic dysregulation of B and CD4⁺ T cells at baseline was detected in patients with acute infected and poor CD4⁺ T-cell recovery. Proteomics analysis revealed distinct temporal regulation profiles of both T helper cells and B cells between IRs and INRs among patients with acute infection. Our results suggest that the functions of memory B cells in INRs are dysregulated at the early stage of ART, possibly through disruption of Tfh cell function. The frequency and function of Tfh cells and their subsets are potential predictors of poor immune recovery.

Keywords: HIV-1; T follicular helper cells; immune recovery; immune responses; incomplete immune reconstitution; memory B cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HIV
HIV Infections*
Humans
Memory B Cells
Proteomics
T Follicular Helper Cells
T-Lymphocytes, Helper-Inducer