Association of circulatory Tfh-like cells with neutralizing antibody responses among chronic HIV-1 subtype C infected long-Term nonprogressors and progressors

Chinnambedu Ravichandran Swathirajan, Pannerselvam Nandagopal, Ramachandran Vignesh, Aylur Kailasam Srikrishnan, Rajat Goyal, Huma Qureshi, Shanmugam Saravanan, Sunil Solomon, Luke Elizabeth Hanna, Munusamy Ponnan Sivasankaran, Nikhil Singla, Joyeeta Mukherjee, Shweta Chatrath, Jakub Kopycinski, Kailapuri Gangatharan Murugavel

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3-circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-Term nonprogressors (LTNP)-19; Progressors-13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3-cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3-cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as 'top neutralizers' and 23 as 'low neutralizers' and they did not show any correlations with CXCR3+ and CXCR3-cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3-might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.

Original languageEnglish (US)
Article numberftz044
JournalPathogens and Disease
Volume77
Issue number4
DOIs
StatePublished - Jan 1 2019

Keywords

  • broadly neutralizing antibodies
  • circulatory Tfh-like cells
  • HIV-1 neutralizers
  • MPER binding antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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