Altered ratio of t follicular helper cells to t follicular regulatory cells correlates with autoreactive antibody response in simian immunodeficiency virus–Infected rhesus macaques

Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (T FH ) cells, and T follicular regulatory (T FR ) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of T FH /T FR cells in the GC contributes to the increased prevalence of autoreactive Abs in chronic HIV infection. We tested this hypothesis using a rhesus macaque (RM) SIV model. We measured the frequency of T FH cells, T FR cells, and GC B cells in LTs and anti-dsDNA and anti-phospholipid Abs from Indian RMs, with and without SIV infection. We found that the frequency of anti-dsDNA and anti-phospholipid Abs was much higher in chronically infected RMs (83.3% [5/6] and 66.7% [4/6]) than in acutely infected RMs (33.3% [2/6] and 18.6% [1/6]) and uninfected RMs (0% [0/6] and 18.6% [1/6]). The increased ratio of T FH /T FR cells in SIV infection correlated with anti-dsDNA and anti-phospholipid autoreactive Ab levels, whereas the frequency of T FR cells alone did not correlate with the levels of autoreactive Abs. Our results provide direct evidence that the ratio of T FH /T FR cells in LTs is critical for regulating autoreactive Ab production in chronic SIV infection and possibly, by extension, in chronic HIV-1 infection. The Journal of Immunology, 2018, 200: 3180–3187.

Original languageEnglish (US)
Pages (from-to)3180-3187
Number of pages8
JournalJournal of Immunology
Volume200
Issue number9
DOIs
StatePublished - May 1 2018

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Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
Macaca mulatta
Antibody Formation
Germinal Center
Lymphoid Tissue
HIV Infections
Phospholipids
HIV-1
B-Lymphocytes
Infection
Allergy and Immunology
HIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Altered ratio of t follicular helper cells to t follicular regulatory cells correlates with autoreactive antibody response in simian immunodeficiency virus–Infected rhesus macaques. / Fan, Wenjin; Demers, Andrew James; Wan, Yanmin; Li, Qingsheng.

In: Journal of Immunology, Vol. 200, No. 9, 01.05.2018, p. 3180-3187.

Research output: Contribution to journalArticle

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abstract = "Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (T FH ) cells, and T follicular regulatory (T FR ) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of T FH /T FR cells in the GC contributes to the increased prevalence of autoreactive Abs in chronic HIV infection. We tested this hypothesis using a rhesus macaque (RM) SIV model. We measured the frequency of T FH cells, T FR cells, and GC B cells in LTs and anti-dsDNA and anti-phospholipid Abs from Indian RMs, with and without SIV infection. We found that the frequency of anti-dsDNA and anti-phospholipid Abs was much higher in chronically infected RMs (83.3{\%} [5/6] and 66.7{\%} [4/6]) than in acutely infected RMs (33.3{\%} [2/6] and 18.6{\%} [1/6]) and uninfected RMs (0{\%} [0/6] and 18.6{\%} [1/6]). The increased ratio of T FH /T FR cells in SIV infection correlated with anti-dsDNA and anti-phospholipid autoreactive Ab levels, whereas the frequency of T FR cells alone did not correlate with the levels of autoreactive Abs. Our results provide direct evidence that the ratio of T FH /T FR cells in LTs is critical for regulating autoreactive Ab production in chronic SIV infection and possibly, by extension, in chronic HIV-1 infection. The Journal of Immunology, 2018, 200: 3180–3187.",
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