Human T follicular helper (Tfh) cells and disease

Abstract

The generation of protective antibodies by B cells following natural infection or vaccination requires ‘help’ from CD4+ T cells. T follicular helper (Tfh) cells are the specialized CD4+ T cell subset that has evolved the appropriate mechanisms to induce the activation and differentiation of B cells into immunoglobulin (Ig) secreting cells. As such, appropriate control of Tfh cell generation and function is essential to human health as overactivation is likely to result in autoimmunity, whereas underactivation is often associated with immunodeficiency. Furthermore, an understanding of the regulation of these cells may be invaluable to improved vaccine development strategies. Traditionally Tfh cells have been identified by their anatomical location in secondary lymphoid tissues, which has hindered the study of these cells in humans as access to these tissues is often not feasible. However, recent studies have identified the circulating counterparts to tissue Tfh cells and with this has come a wealth of knowledge gained from the study of these cells in human disease. Here we review some of the recent developments on the role of human Tfh cells in health and disease.

Association of circulating follicular helper T cells with disease course of NMO spectrum disorders

“…Although the definite pathogenesis is not clear, AQP4-Ab based antibody-dependent cellmediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) process in the pathogenesis has been reported as consistent with the pathological lesions in NMO patients (Ma and Deenick, 2014;Misu et al, 2013). Here, we found Tfh cells increased in NMOSD patients and Tfh cell population was associated with disease activity.…”

TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization

“…12,16,20,23,24 Several cT FH subsets have been reported, each displaying drastically different functions. 25 For example, cT FH subsets harboring T H 1-, T H 2-and T H 17-like effector functions have been identified in humans, with T H 2-and T H 17-like cT FH being more efficient in inducing B cells to produce IgG than T H 1-like cT FH . 12 T follicular helper cells are the main CD4 + T cells specialized in supporting B-cell responses, but their role in driving transfusion-associated alloimmunization is not fully characterized.…”

Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes

“…12 Tfh cells are abnormally regulated in several inherited and acquired diseases. 13,14 Expansion of dysfunctional Tfh cells is a major contributor to systemic autoimmunity, including systemic lupus erythematosus (SLE; lupus), Sjogren syndrome, and rheumatoid arthritis. 15,16 Their malignant transformation results in the phenotype of angioimmunoblastic T-cell lymphoma (AITL), a subset of peripheral T-cell lymphoma (PTCL).…”