High Levels Of CXCR5 Research Articles

Whole-blood phenotyping to assess alloimmunization status in transfused sickle cell disease patients

AbstractIt is essential to limit hemolytic transfusion reactions in polytransfused individuals, and the prevention of alloimmunization is a key solution. CD4+ T lymphocyte (TL) markers, particularly follicular T helper (Tfh) cells, may differentiate between responder and nonresponder alloimmunization statuses. We tested this hypothesis by studying the phenotype of CXCR5+PD1+ TLs in whole blood. Our results suggest that high levels of CXCR5+PD1+CD4+ TLs in whole blood may be a characteristic of nonalloimmunized patients. However, these cells did not display the phenotypic characteristics of active Tfh cells. Instead, a decrease in blood quiescent Tfh-cell levels was observed in nonalloimmunized polytransfused patients. High levels of CXCR5+PD1+CD4+ TLs may be associated with inhibitory signaling functions of T cells, as reflected by the low levels of PD1+ICOS+ cells in the nonalloimmunized polytransfused group. The description of these particular phenotypes, and their comparison among groups of patients, responders, and nonresponders, suggests that new immunological components should be considered when trying to understand posttransfusion alloimmunization.

High CXCR3 on Leukemic Cells Distinguishes IgHV mut from IgHV unmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones.

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5high and CD5low neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n = 60) subgrouped according to the IgHV mutational status (IgHVmut, n = 24; IgHVunmut, n = 36). CD5high subpopulation showed a high percentage of CXCR3 (P < 0.001), CCR10 (P = 0.001), and CD62L (P = 0.031) and high levels of CXCR5 (P = 0.005), CCR7 (P = 0.013) compared to CD5low cells expressing high CXCR4 (P < 0.001). Comparing IgHVmut and IgHVunmut patients, high levels of CXCR3 on CD5high and CD5low subpopulations were detected in the IgHVmut patients, with better discrimination in CD5low subpopulation. Levels of CXCR3 on CD5low subpopulation were associated with time to the next treatment, thus further confirming its prognostic value. Taken together, our analysis revealed higher CXCR3 expression on both CD5high and CD5low neoplastic cells in IgHVmut with a better prognosis compared to IgHVunmut patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.

Abstract P4-06-12: Biological characteristics and prognostic value of Tfh-like cells in the tumor tissue of breast cancer

Abstract Objective T follicular helper (Tfh) cells formed in germinal center are a distinct subpopulation of CD4+ T cell, with high levels of CXCR5, ICOS, PD-1, Bcl-6 and CXCL13 as their characteristic markers. Secreting IL-21 and helping humoral response are their key features. They have been identified in different types of tumors. However, it still remains unclear in breast cancer. Researches of them may provide new clues to the diagnosis and treatment of breast cancer, especially for the potential immunotherapies. This study was performed to explore the existence and a possible role of Tfh cells in breast cancer. Method Freshly resected invasive breast cancer tissue from Fudan University Shanghai Cancer Center (FUSCC) were collected, with 27 samples for identifying the presence, phenotype and cytokine-producing capacity of Tfh-like cells and 386 for exploring the correlation between Tfh-like cells and clinicopathological characteristics in breast cancer during 03/2015 to 05/2017. Of all those 386 samples, patients were divided into Luminal A (N=61), Luminal B (HER2-) (N=138), Luminal B (HER2+) (N=72), HER2+ (non-luminal) (N=57) and triple negative (N=58) based on St Gallen International Expert Consensus. Data was analyzed based on the result from Multiparameter Flow Cytometry. The correlation between Tfh-like cells and clinicopathological characteristics in breast cancer was examined with t test or one way ANOVA with Tukey's multiple comparisons test. Results A subpopulation of PD1hiCD4+ T cells in tumor tissues of breast cancer was identified as Tfh-like cells, with the specific expression of Bcl-6 and CXCL13. Phenotypes of those cells were checked by flow cytometry. They were of a high level of ICOS but negative for CXCR5, suggesting that they were atypical Tfh cells. They had high levels of activated molecules such as CD38, CD71, CD95 and HLADR, showing that they were highly activated. They had high levels of suppressive markers as Tim3, TIGIT, and LAG3, indicating they could have regulatory functions. In addition, Tfh-like cells specifically secreted cytokine IL-21 with stimulation. Data showed that high grade (N=166; mean±SEM, 17.62±0.87) compared with low grade (N=220; mean±SEM, 12.41±0.46) or high Ki-67 level (N=300; mean±SEM, 15.38±0.58) with low Ki-67 level (N=86; mean±SEM, 12.10±0.67), and negative ER expression (N=115; mean±SEM, 17.47±1.05) compared with positive ER expression (N=271; mean±SEM, 13.46±0.50) or negative PR expression (N=177; mean±SEM, 16.87±0.83) compared with positive PR expression (N=209; mean±SEM, 12.77±0.50) was associated with higher frequency of Tfh-like cells (P&amp;lt;0.01 to all). Patients with triple negative had higher frequency of Tfh-like cells than those with Luminal A (difference, 6.83; P=0.0006) and Luminal B (HER2-) (difference, 4.61; P=0.0124). Patients with HER2+ (non-luminal) had higher frequency of Tfh-like cells than those with Luminal A (difference, 5.34; P=0.0146). These results indicate that higher frequency of Tfh-like cells could have negative prognostic influence. Conclusion Our study defined a PD1hiBcl6+CXCL13+CD4+ T cell subpopulation, which specifically secretes cytokine IL-21 as Tfh-like cells. Higher frequency of Tfh-like cells is more likely to be seen in patients with poor prognosis. Citation Format: Ma L-X, Guo L, Goswami S, Li T, Cao C-M, Zhang X-m, Wu J. Biological characteristics and prognostic value of Tfh-like cells in the tumor tissue of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-12.

IL-4 producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells

Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced by CD4(+) T cells in response to helminth infection. IL-4 not only promotes the differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and IgE isotype-switched antibody responses. Despite the IL-4-mediated link between Th2 cells and B lymphocytes, the location of IL-4-producing T cells in the lymph nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2 response and IL-4 production in the draining mesenteric lymph nodes during infection with the enteric nematode Heligmosomoides polygyrus. We show that although IL-4-competent Th2 cells are found throughout the B and T cell areas, IL-4-producing Th2 cells are restricted to the B cell follicles and associate with germinal centers. Consistent with their localization, IL-4 producers express high levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and maturation. Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo.