Background: In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL). Patients and Methods: 24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3–/NKp30+ and CD56+/CD3–/Tim-3+ cells was determined by multicolor flow cytometry. Results: Our results revealed that Tim-3 is significantly upregulated on natural killer (NK) cells of CLL patients in comparison to healthy controls. NK cells of CLL patients showed lower expression of NKp30-activating receptor compared to controls. Tim-3 expression pattern on NK cells of CLL patients was correlated with poor prognostic factors including low hemoglobin level, high absolute lymphocyte count, and high serum C-reactive protein level. Conclusion: Dysregulated expression of Tim-3 and NKp30 receptors confirms the exhaustion state of NK cells in CLL. Our data introduce Tim-3 as a promising biomarker and potential target for immunotherapy of CLL.
MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.
Journal homepage: www.zums.ac.ir/jhehp Background: One of the challenges of implementing the family physician program is the decrease in the number of doctors, especially in rural and deprived areas, the present study aimed to determine the intentions of family physicians to persist in the health centers affiliated in Hormozgan city. Methods: This cross-sectional study was conducted on 195 physicians in the health centers implementing the family physician program. Data were collected using a questionnaire. Data analysis was performed in SPSS version 21 using independent t-test, Pearson's correlation-coefficient, and ANOVA. Results: In total, 57.9% of the participants were female, and 42.1% were male. The majority of the subjects (61%) were aged 30-60 years. The results of Pearson's correlationcoefficient indicated that income, payment status, working hours, willingness to continue education, job security, motivation to serve, commitment to service provision, and confidence in the family physician program had significant, positive associations with the intentions of family physicians to stay in the health centers (P < 0.001). Conclusion: According to the results, health ministers, policymakers, and planners could help with the persistence of family physicians in the healthcare centers in deprived areas through reviewing the number of the healthcare team members and their job descriptions.
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