CXCR5+ CD8 T Cells: Protective or Pathogenic?

Abstract

CD8 T cells are infrequently considered part of germinal center reactions. Yet, a distinct CXCR5+ CD8 T cell subset identified within the B cell follicle and germinal center in situations of chronic antigen has recently been defined. CXCR5+ CD8 T cells maintain transcriptional and phenotypic features consistent with the CD8 T cell nomenclature of a non-exhausted, effector memory population. CD8 T cell localization to the B cell follicle suggests a functional profile similar to CD4 T follicular helper cells that are licensed to promote B cell responses. The functional mechanisms defined under different immune settings, while largely similar, differentially control disease pathogenesis. CXCR5+ CD8 T cells control viral load during infection, and also promote antibody-mediated autoimmune disease progression. The existence of this novel CXCR5+ CD8 T cell subset in human and murine models of disease may provide a paradigm shift in our understanding of germinal center reactions.

Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5 + CD8 + T cell abundance

“…Corresponding to the previous studies in circumstances of viral infection and tumor infiltration, we confirm the selfrenewal and effector memory-like phenotype of CXCR5 + CD8 + T cells in MIBC. 17,26 Intriguingly, we discovered that CXCR5 + CD8 + T cells expressed activated TCF1 (transcripted by TCF7) compared to its CXCR5 − CD8 + T cells counterpart. Meanwhile, it is reported that TCF7 + identified a subset of superior survival-indicating CD8 + T cells in melanoma, 36 which is consistent with our results.…”

“…In the TCGA Cohort, the CXCR5 + CD8 + T signature score was comprised of the mean value of the mRNA expression of CD8A, CXCR5, CXCR3, ICOS, CD27, IL21, TNF, TNFRSF6B, PDCD1, TBX21, SLAMF6, and IL27RA. 17,26 To control the range of the CXCR5 + CD8 + T signature score, the mRNA expression was pre-calculated with log 2 (x + 1). The gene constitution of multiple signatures was provided in Supplementary Table 3.…”

“…15,16 Remarkably, CXCR5 + CD8 + T cells are reported to display a rather important role in immune response against tumor after further investigation. 17 In cases of B cell lymphoma, a trend of CXCR5 + CD8 + T cells directly targeting tumor cells was observed. 18 In HBV-related liver cancer, CXCR5 + CD8 + T cells are likely to be initially induced by viral responses, and then act on tumor cells.…”

A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target

“…CXCR5, which is expressed in Tfh cells, mature B cells, and Treg cells, is involved in B cell migration and the formation of germinal cells (GCs) and guides disease-causing double negative (DN) T cells into lymphoid organs and kidneys ( 43 ). In CXCR5-deficient lupus murine model, the migration of DN T cell to lymph nodes was reduced and the kidney was not infiltrated ( 44 ).…”

Does B Cell Follicle Exclusion of CD8+ T Cells Make Lymph Nodes Sanctuaries of HIV Replication?

“…Several studies have demonstrated a population of CXCR5 + CD8+ T cells within B cell follicles. These cells have been shown to have different transcriptional profiles from their CXR5-CD8+ T cell counterparts and their role in controlling viral replication has been the subject of many recent studies (70, 71). It has been shown that increased CXCR5+ effector CD8+ T cells in secondary lymphoid tissue is associated with increased control of chronic viral infections, including HIV (66, 72, 73).…”