FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability

León, Beatriz; Bradley, John E.; Lund, Frances E.; Randall, Troy D.; Ballesteros-Tato, André

doi:10.1038/ncomms4495

Cited by 136 publications

(138 citation statements)

References 55 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…Interestingly, work in animal models revealed that IL-2 suppresses the differentiation of T follicular helper cells and negatively impacts influenza-specific long-lived antibody responses, a finding consistent with our observation (30,31). The strength and consistency of our finding of a particular subset of cytokine-secreting Determining the immunologic basis for long-term antibody persistence is particularly important for vaccination strategies.…”

Section: Il-21supporting

confidence: 80%

Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection

Sridhar

Begom

Höschler

et al. 2015

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Antibodies to influenza hemagglutinin are the primary correlate of protection against infection. The strength and persistence of this immune response influences viral evolution and consequently the nature of influenza epidemics. However, the durability and immune determinants of induction of humoral immunity after primary influenza infection remain unclear.Objectives: The spread of a novel H1N1 (A[H1N1]pdm09) virus in 2009 through an unexposed population offered a natural experiment to assess the nature and longevity of humoral immunity after a single primary influenza infection.Methods: We followed A(H1N1)pdm09-seronegative adults through two influenza seasons (2009-2011) as they developed A(H1N1)pdm09 influenza infection or were vaccinated. Antibodies to A(H1N1)pdm09 virus were measured by hemagglutinationinhibition assay in individuals with paired serum samples collected preinfection and postinfection or vaccination to assess durability of humoral immunity. Preexisting A(H1N1)pdm09-specific multicytokine-secreting CD4 and CD8 T cells were quantified by multiparameter flow cytometry to test the hypothesis that higher frequencies of CD4 1 T-cell responses predict stronger antibody induction after infection or vaccination.Measurements and Main Results: Antibodies induced by natural infection persisted at constant high titer for a minimum of approximately 15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titer after infection was inversely correlated to the frequency of preexisting circulating A(H1N1)pdm09-specific CD4 1 IL-2 1 IFN-g 2 TNF-a 2 T cells (r = 20.4122; P = 0.03).Conclusions: The longevity of protective humoral immunity after influenza infection has important implications for influenza transmission dynamics and vaccination policy, and identification of its predictive cellular immune correlate could guide vaccine development and evaluation.

show abstract

Section: Il-21supporting

confidence: 80%

Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection

Sridhar

Begom

Höschler

et al. 2015

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Our Based on our data, we hypothesize that CXCL13 expression by BC TIL can be influenced by Treg consumption and control of IL2 availability, an effect exhibited during murine T FH cell differentiation and GC responses to influenza infection (30). This idea is further supported by the dramatic increases in CXCL13 we detected in IL2-deprived D-PB CD4 + T cells.…”

Section: Discussionsupporting

confidence: 67%

“…The work reported here and our other recent experiments (data not shown) found that IL2 deprivation is critical for CXCL13 induction, with TGFβ1 providing a synergistic signal only. IL2 has previously been found to negatively regulate T FH cell differentiation (29), while IL2 consumption by Tregs was shown to be essential for murine T FH development and the subsequent GC response (30). This data suggest that the balance between these CD4 + subpopulations is influenced by their surrounding microenvironment.…”

Section: Cd3 + Cd4mentioning

confidence: 58%

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

Gu-Trantien¹,

Migliori²,

Buisseret³

et al. 2017

JCI Insight

297

283

View full text Add to dashboard Cite

“…In addition, in the [DBA/ 2→BALB/c] cGVHD murine model, which develops both SScand SLE-type symptoms, add-back of Tregs caused a limited reduction of anti-dsDNA autoantibody compared with sclerodermatous skin damage (35). A recent report shows that Treg depletion severely reduces follicular Th cells and germinal center B cell responses to influenza virus (53). Consistent with this report, in our study, the donor follicular Th cell population in CD28TM-Tg hosts was lower than in WT hosts (data not shown).…”

Section: Discussionsupporting

confidence: 82%

Defects in Regulatory T Cells Due to CD28 Deficiency Induce a Qualitative Change of Allogeneic Immune Response in Chronic Graft-versus-Host Disease

Akieda

Wakamatsu

Nakamura

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

In patients receiving allogeneic hematopoietic cell transplantation, chronic graft-versus-host disease (cGVHD) remains a frequent complication and resembles autoimmune diseases such as systemic lupus erythematosus and systemic sclerosis. Our previous work demonstrated the critical role of CD28 costimulation of donor T cells for GVHD induction. In this study, we investigate the role of CD28 costimulation of host T cells in cGVHD. CD28-intact mice as hosts showed systemic lupus erythematosus–type cGVHD, whereas CD28-deficient mice developed a distinct phenotype of cGVHD, with fibrotic damage in skin and internal organs, resembling systemic sclerosis. This phenotype was due to a lack of signaling through the C-terminal proline-rich motif within host CD28’s cytoplasmic tail, a motif previously shown to be required for development of regulatory T cells (Tregs) and function of conventional T cells. Adoptive transfer experiments demonstrated that a defect in host CD4+CD25+ Tregs, but not in conventional T cells, was responsible for disease phenotype. Host Treg deficiency altered the cytokine pattern of donor CD4+ T cells and the Ag specificity of autoantibodies, and these might lead to phenotypic change. Thus, host CD28 signaling controlled the pathogenesis of cGVHD through effects on host Tregs, whose status impacts qualitatively on the allogeneic immune responses.

show abstract

FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability

Cited by 136 publications

References 55 publications

Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection

Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

Defects in Regulatory T Cells Due to CD28 Deficiency Induce a Qualitative Change of Allogeneic Immune Response in Chronic Graft-versus-Host Disease

Contact Info

Product

Resources

About