Anti-CD40 monoclonal antibody, clone IC25 [APC]

Humanized NOD/SCID/IL-2 receptor gamma-chains(null) (huNSG) mice recapitulate some features of human T-cell populations that can be exploited in basic and pre-clinical research. CXCR5(+) T CD8(+) T-cells play an important role in the control of viral infections and tumors. Indeed, they have been associated with low-level HIV replication, making them a possible novel correlate of protection, and potentially useful in the eradication of HIV reservoirs. Here, by flow cytometry, we evaluated the reconstitution of CXCR5(+) CD8(+) T-cells in huNSG mice engrafted with CD34(+) hematopoietic stem cells. This population was readily generated in huNSG mice, and where particularly confined to spleen and lymph nodes. These cells exhibited a follicular-like phenotype, with expression of Programmed Death (PD)-1, Inducible T-cell costimulatory (ICOS), and absence of CCR7. Moreover, CXCR5(+) CD8(+) T-cells had a higher expression of interleukin (IL)-21 and a higher cytotoxic potential compared with CXCR5(-) cells. HIV infection did not affect the frequencies of CXCR5(+) CD8(+) T-cells in secondary lymphoid organs. Finally, taking advantage of the high proportion of naive T-cells in huNSG mice, we evaluated the in vitro response of splenic T-cells to the follicular profile-polarizing cytokines Transforming Growth Factor (TGF)-beta 1 and IL-23. After in vitro treatment, there was an increase in CXCR5(+) CD8(+) T-cells, which exhibited high levels of PD-1, CD40 L and low expression of CCR7. Thus, there is a reconstitution of CXCR5(+) CD8(+) T-cells in huNSG mice, supporting the use of this model for exploring the biology and role of this cell population in healthy and diseased conditions.

Discontinuation of nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) remains a global but controversial problem. Clinical outcomes of NA cessation depend on the interplay between viral factors and host immunity. Recent studies have shown that genetic polymorphisms might influence the immune response in chronic HBV infection. A total of 33 single-nucleotide polymorphisms (SNPs) from 16 genes (BCL6, CD40, CD40L, CTLA-4, CXCL13, CXCR5, ICOS, IL-21, HLA-C, NTCP, UBE2L3, STAT4, IFN-lambda 3, CYP27B1, INST10, and IPS1) were selected and analyzed in 106 CHB patients enrolled in an off-treatment cohort. Significantly unbalanced distributions between patients who experienced clinical relapse and those who did not were found regarding two SNPs, rs676925 in CXCR5 and rs733618 in CTLA-4. Furthermore, the genotype 'GC' of rs676925 were associated with decreased risk of clinical relapse, implicating that rs676925 may serve as a protective factor for HBV control and facilitate a virus-specific immune response. We also compared the expression of CXCR5 in lymphocytes and its ligand CXCL13 in plasma between different genotypes of rs676925. However, no significant differences were observed. In conclusion, this study suggested that the rs676925 'GC' genotype of the CXCR5 gene were associated with decreased risk of clinical relapse after discontinuation of long-term NA therapy in CHB patients.