Association of circulatory Tfh-like cells with neutralizing antibody responses among chronic HIV-1 subtype C infected long-term nonprogressors and progressors. Issue 4 (23rd August 2019)

• Record Type: Journal Article
• Authors: Swathirajan, Chinnambedu Ravichandran; Nandagopal, Pannerselvam; Vignesh, Ramachandran; Srikrishnan, Aylur Kailasam; Goyal, Rajat; Qureshi, Huma; Saravanan, Shanmugam; Solomon, Sunil Suhas; Hanna, Luke Elizabeth; Sivasankaran, Munusamy Ponnan; Singla, Nikhil; Mukherjee, Joyeeta; Chatrath, Shweta; Kopycinski, Jakub; Murugavel, Kailapuri Gangatharan
• Is Part Of: Pathogens and disease. Volume 77:Issue 4(2019)
• Publication Date: 2019-08-23
• Subjects: circulatory Tfh-like cells -- broadly neutralizing antibodies -- MPER binding antibodies -- HIV-1 neutralizers; Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1093/femspd/ftz044
• Languages: English
• ISSNs: 2049-632X

Abstract

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. Abstract : This study addresses the correlation between Tfh subsets and breadth of neutralization in progressors and non-progressors HIV-infected individuals, showing a positive correlation between CXCR3+ Tfh cells and broadly neutralizing anti-HIV antibodies.