Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion

By R. Morita, N. Schmitt, S. Bentebibel, R. Ranganathan, L. Bourdery, G. Zurawski, E. Foucat, M. Dullaers, SangKon Oh, Natalie Sabzghabaei and 5 more. Immunity, 2011

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Although a fraction of human blood memory CD4+ T cells expresses chemokine (C-X-C motif) receptor 5 (CXCR5), their relationship to T follicular helper (Tfh) cells is not well-established. Here we show that human blood CXCR5+ CD4+ T cells share functional properties with Tfh cells, and appear to represent their circulating memory compartment. Blood CXCR5+ CD4+ T cells comprised three subsets; T helper 1 (Th1), Th2 and Th17 cells. Th2 and Th17 cells within CXCR5+, but not within CXCR5−, compartment efficiently induced naïve B cells to produce immunoglobulins via interleukin-21 (IL-21). In contrast, Th1 cells from both CXCR5+ and CXCR5− compartments lacked the capacity to help B cells. Patients with juvenile dermatomyositis, a systemic autoimmune disease, displayed a profound skewing of blood CXCR5+ Th subsets towards Th2 and Th17 cells. Importantly, the skewing of subsets correlated with disease activity and frequency of blood plasmablasts. Collectively, our study suggests that an altered balance of Tfh subsets contributes to human autoimmunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/f6b67d9cc15a16d203dad686a24304f77ca26497

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Citations in the corpus

T follicular helper cell biology: A decade of discovery and diseases (2019, background): “The large majority of flu-specific activated cTfh cells are CXCR3+ and CXCR3+ cTfh cells correlate with acute anti-influenza IgG (Bentebibel et al., 2013); however, CXCR3+ memory cTfh cells are particularly poor providers of B cell help in vitro (Locci et al., 2013; Morita et al., 2011).”
Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses (2013, positive): “That observation was unexpected, given that Morita and colleagues demonstrated that CXCR3+CXCR5+ cells are the worst CXCR5+CD4+ T cells at helping B cells (Morita et al., 2011), and we have confirmed that finding here.”
Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis. (2015, background): “Circulating TFH cells are hypothesized to be counterparts of tonsillar TFH cells (Morita et al., 2011; Schmitt et al., 2014), easing Frequency of Extrafollicular Memory TFH Cells with Age see Table S2). llar CXCR5+ TFH cells (P1–P4).”
T follicular helper cell differentiation, function, and roles in disease (2014, background): “, 2013), juvenile dermatomyositis (Morita et al., 2011), and systemic lupus erythematosus (He et al.”
Cancer immunotherapy via dendritic cells (2012, positive): “In contrast, Tfh1 cells have been found to lack the capacity to help naı̈ve B cells [35].”
Induction of ICOS+CXCR3+CXCR5+ TH Cells Correlates with Antibody Responses to Influenza Vaccination (2013, background): “We have previously shown that human blood CXCR5CD4 T cells are composed of subsets that differentially express the chemokine receptors CXCR3 and CCR6, and display different functions (28).”
Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production (2013, methodology): “Sorted CD4 T cell populations (105 cells) were co-cultured with sorted autologous B cell populations (105 cells) in the presence of 250 ng/ml SEB (Sigma-Aldrich) in 96-well U-bottom plates as previously described (Morita et al., 2011).”
Follicular Helper T Cells. (2016, background): “Human cTfh cells can also be stratified into distinct cytokine-producing subsets by their expression of CXCR3 and CCR6: CXCR3+CCR6-Th1 type, CXCR3-CCR6+-Th17 type, and CXCR3-CCR6-Th2 type (62).”