Dataset Information

Mapping the Lineage Relationship between CXCR5+ and CXCR5- CD4+ T Cells in HIV-Infected Human Lymph Nodes.

ABSTRACT: CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5- CD4+ T cells with TFH-cell-like features. This CXCR5- subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5-PD-1+ICOS+ T cells revealed a shared clonal relationship with TFH cells. CXCR5-PD-1+ICOS+ T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5-PD-1+ICOS+ T cells to circulating CXCR5- CD4+ T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation.

SUBMITTER: Del Alcazar D

PROVIDER: S-EPMC6878759 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Mapping the Lineage Relationship between CXCR5+ and CXCR5- CD4+ T Cells in HIV-Infected Human Lymph Nodes.

Del Alcazar Daniel D Wang Yifeng Y He Chenfeng C Wendel Ben S BS Del Río-Estrada Perla M PM Lin Jerome J Ablanedo-Terrazas Yuria Y Malone Michael J MJ Hernandez Stefany M SM Frank Ian I Naji Ali A Reyes-Terán Gustavo G Jiang Ning N Su Laura F LF

Cell reports 20190901 12

CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5- CD4+ T cells with TFH-cell-like features. This CXCR5- subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell r ...[more]

PMID: 31533030

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Project description:The near-infrared (NIR) fluorescence axillary reverse mapping (ARM) procedure is a promising tool to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND). The ARMONIC clinical trial was conducted to validate the technique on a large cohort of patients and to analyze the predictive clinical factors for ARM lymph node metastasis. For the first time, the fluorescence signal intensity from the ARM lymph nodes was measured and correlated with clinical findings. A total of 109 patients with invasive breast cancer and indications of mastectomy and ALND underwent the NIR fluorescence ARM procedure. Indocyanine green was administered by intradermal injection followed by intraoperative identification and resection of the ARM lymph nodes with NIR fluorescence camera guidance. The fluorescence signal intensity and signal distribution were then measured ex vivo and compared with clinical outcomes. ARM lymph nodes were successfully identified by fluorescence in 94.5% of cases. The mean normalized fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes (p = 0.3728). At the microscopic level, the fluorescence signal distribution was focally intense in lymphoid tissue areas. Only the preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with a higher ARM node fluorescence signal intensity (p = 0.0253), though it was not significantly associated with the pathological nodal (pN) status (p = 0.8081). Based on an optimal cut-off fluorescence value, the final sensitivity and specificity of the NIR fluorescence ARM procedure for ARM lymph node metastatic involvement were 64.7% and 47.3%, respectively. Although our preliminary results did not show that fluorescence signal intensity is a reliable diagnostic tool, the NIR fluorescence ARM procedure may be useful for ARM lymph node identification. Clinical trial registration: NCT02994225.

Dataset Information

Mapping the Lineage Relationship between CXCR5+ and CXCR5- CD4+ T Cells in HIV-Infected Human Lymph Nodes.

Publications

Mapping the Lineage Relationship between CXCR5<sup>+</sup> and CXCR5<sup>-</sup> CD4<sup>+</sup> T Cells in HIV-Infected Human Lymph Nodes.

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