Induction of ICOS+CXCR3+CXCR5+ TH Cells Correlates with Antibody Responses to Influenza Vaccination.
ABSTRACT Seasonal influenza vaccine protects 60 to 90% of healthy young adults from influenza infection. The immunological events that lead to the induction of protective antibody responses remain poorly understood in humans. We identified the type of CD4(+) T cells associated with protective antibody responses after seasonal influenza vaccinations. The administration of trivalent split-virus influenza vaccines induced a temporary increase of CD4(+) T cells expressing ICOS, which peaked at day 7, as did plasmablasts. The induction of ICOS was largely restricted to CD4(+) T cells coexpressing the chemokine receptors CXCR3 and CXCR5, a subpopulation of circulating memory T follicular helper cells. Up to 60% of these ICOS(+)CXCR3(+)CXCR5(+)CD4(+) T cells were specific for influenza antigens and expressed interleukin-2 (IL-2), IL-10, IL-21, and interferon-γ upon antigen stimulation. The increase of ICOS(+)CXCR3(+)CXCR5(+)CD4(+) T cells in blood correlated with the increase of preexisting antibody titers, but not with the induction of primary antibody responses. Consistently, purified ICOS(+)CXCR3(+)CXCR5(+)CD4(+) T cells efficiently induced memory B cells, but not naïve B cells, to differentiate into plasma cells that produce influenza-specific antibodies ex vivo. Thus, the emergence of blood ICOS(+)CXCR3(+)CXCR5(+)CD4(+) T cells correlates with the development of protective antibody responses generated by memory B cells upon seasonal influenza vaccination.
- SourceAvailable from: Rakesh Kumar Bhat[Show abstract] [Hide abstract]
ABSTRACT: Author Summary Infection with influenza viruses is associated with high morbidity and mortality. Therefore, vaccination is recommended in immunosuppressed patients, however often the post-vaccine induced protection is insufficient. Factors associated with reduced vaccine responses may guide preventive strategies and could offer novel targets for adjuvants. Here, we explore the impact of IL-28B on B- and T-cell responses during vaccination. We found that a single nucleotide polymorphism (minor allele genotype) in the IL-28B gene was associated with a significant increase in the antibody seroconversion rate following influenza vaccination. Interestingly, this SNP reduces the expression of IL-28B. In addition, in vitro stimulation of peripheral blood mononuclear cells from patients with the SNPs had increased IL-4 production in CD4 T-cells. As a potential mechanism, we show that recombinant IL-28B inhibits influenza stimulated Th2 cytokine release, B-cell activation/prolPLoS Pathog. 12/2014; 10:e1004556.
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ABSTRACT: Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.PLoS ONE 10/2014; 9(10):e111098. · 3.53 Impact Factor
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ABSTRACT: HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B-cells, and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely, regulatory T cells (Tregs) and T follicular helper cells (Tfh). These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B-cell hyperplasia and increased germinal center activity. Antiretroviral therapy may reduce the lymphocyte activation, but not completely, and therefore, there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B-cell, or Treg dysfunction.Frontiers in Immunology 01/2014; 5:681.