Subspecialization of Cxcr5+ T Cells

By Chang H. Kim, L. Rott, I. Clark‐Lewis, D. Campbell, Lijun Wu, E. Butcher. Journal of Experimental Medicine, 2001

596 citations recorded by the source corpus.

The T helper (Th) cell pool is composed of specialized cells with heterogeneous effector functions. Apart from Th1 and 2 cells, CXCR5+ T cells have been suggested to be another type of effector T cell specialized for B cell help. We show here that CXCR5+ T cells are heterogeneous, and we identify subsets of CXCR5+ CD4 T cells that differ in function and microenvironmental localization in secondary lymphoid tissues. CD57+CXCR5 T cells, hereafter termed germinal center Th (GC-Th) cells, are localized only in GCs, lack CCR7, and are highly responsive to the follicular chemokine B lymphocyte chemoattractant but not to the T cell zone EBI1-ligand chemokine. Importantly, GC-Th cells are much more efficient than CD57−CXCR5+ T cells or CXCR5− T cells in inducing antibody production from B cells. Consistent with their function, GC-Th cells produce elevated levels of interleukin 10 upon stimulation which, with other cytokines and costimulatory molecules, may help confer their B cell helper activity. Our results demonstrate that CXCR5+ T cells are functionally heterogeneous and that the GC-Th cells, a small subset of CXCR5+ T cells, are the key helpers for B cell differentiation and antibody production in lymphoid tissues.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/996c8d228fd6f0d7c05cd16d99e137a9d319cc0d

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Citations in the corpus

Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production (2013, background): “…et al., 2009) is the primary marker of Tfh cells, whereas other markers, such as CXCR5 (the chemokine receptor for CXCL13), inducible T cell co-stimulator (ICOS), and PD-1 (Breitfeld et al., 2000; Schaerli et al., 2000; Kim et al., 2001; Fazilleau et al., 2009a), are not exclusive of Tfh cells.”
Mapping the Diversity of Follicular Helper T Cells in Human Blood and Tonsils Using High-Dimensional Mass Cytometry Analysis. (2015, background): “Interestingly, CD57 expression is often associated with T cell exhaustion and senescence (Brenchley et al., 2003; Wood et al., 2009), but two studies found that CD57+ TFH cells were highly capable of helping B cells (Kim et al., 2001, 2005; Rasheed et al., 2006).”
T Follicular Helper Cells Express a Distinctive Transcriptional Profile, Reflecting Their Role as Non-Th1/Th2 Effector Cells That Provide Help for B Cells1 (2004, background): “CD57 (together with CXCR5) has been described as one of the most relevant markers for distinguishing human TFH cells (10).”
FOLLICULAR HELPER T CELLS: LINEAGE AND LOCATION (2009, background): “An inital study with CD57 and CXCR5 expression to select human tonsillar GC Tfh cells (Kim et al., 2001) emphasized high amounts of the chemokine CXCL13 as a major attribute of Tfh cells (Kim et al., 2004).”
Cutting Edge: Direct Suppression of B Cells by CD4+CD25+ Regulatory T Cells1 (2005, background): “A human CD57 GC-Th cell subset is specifically present within GCs, and they are highly efficient T helpers in stimulating B cells for production of Igs (3, 17).”
Role of CXCR5 and CCR7 in Follicular Th Cell Positioning and Appearance of a Programmed Cell Death Gene-1High Germinal Center-Associated Subpopulation1 (2007, background): “GC-associated T cells are typically enriched within the T zone distal pole of the GC, known as the light zone, and they express high levels of CXCR5 (8, 11, 12).”
Costimulatory molecule ICOS plays a critical role in the development of TH-17 and follicular T-helper cells by regulating c-Maf expression and IL-21 production (2008, background): “org/molecule/query?afcsid=A001155">A001155 ), which has been linked to the development of T FH cell”