Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Impact of Daily Thermocycles on Hatching Rhythms, Larval Performance and Sex Differentiation of Zebrafish

In the wild, water temperature cycles daily: it warms up after sunrise, and cools rapidly after sunset. Surprisingly, the impact of such daily thermocycles during the early development of fish remains neglected. We investigated the influence of constant vs daily thermocycles in zebrafish, from embryo development to sexual differentiation, by applying four temperature regimens: two constant (24°C and 28°C) and two daily thermocycles: 28:24°C, TC (thermophase coinciding with daytime, and cryophase coinciding with night-time) and 24:28°C, CT (opposite to TC) in a 12:12 h light:dark cycle (LD). Embryo development was temperature-dependent but enhanced at 28°C and TC. Hatching rhythms were diurnal (around 4 h after lights on), but temperature- and cycle-sensitive, since hatching occurred sooner at 28°C (48 hours post fertilization; hpf) while it was delayed at 24°C (96 hpf). Under TC, hatching occurred at 72 hpf, while under CT hatching displayed two peaks (at 70 hpf and 94 hpf). In constant light (LL) or darkness (DD), hatching rhythms persisted with tau close to 24 h, suggesting a clock-controlled "gating" mechanism. Under 28°C or TC, larvae showed the best performance (high growth and survival, and low malformations). The sex ratio was strongly influenced by temperature, as the proportion of females was higher in CT and TC (79 and 83% respectively), contrasting with 28°C and 24°C, which led to more males (83 and 76%). Ovarian aromatase (cyp19a) expression in females was highest in TC and CT (6.5 and 4.6 fold higher than at 28°C, respectively); while anti-müllerian hormone (amh) expression in males increased in testis at 24°C (3.6 fold higher compared to TC) and particularly at 28°C (14.3 fold increase). Taken together, these findings highlight the key role of environmental cycles during early development, which shaped the daily rhythms in fish embryo and larvae, and ultimately influenced sex differentiation

Survival and morbidity in very preterm infants in Shenzhen: a multi-center study

ObjectiveTo analyze survival and morbidity among very preterm infants (VPIs) in Shenzhen and explore factors associated with survival without major morbidity.MethodsBetween January 2022 and December 2022, 797 infants were admitted to 25 neonatal intensive care units in Shenzhen with gestational age (GA) < 32 weeks, excluded discharged against medical advice, insufficient information, and congenital malformation, 742 VPIs were included. Comparison of maternal and neonate characteristics, morbidities, survival, and survival without major morbidities between groups used Mann Whitney U test and X2 test, multivariate logistic regression was used to analyze of risk factors of survival without major morbidities.ResultsThe median GA was 29.86 weeks (interquartile range [IQR], 28.0–31.04), and the median birth weight was 1,250 g (IQR, 900–1,500). Of the 797 VPIs, 721 (90.46%) survived, 53.52% (38 of 71) at 25 weeks’ or less GA, 86.78% (105 of 121) at 26 to 27 weeks' GA, 91.34% (211 of 230) at 28 to 29 weeks' GA, 97.86% (367 of 375) at 30 to 31 weeks' GA. The incidences of the major morbidities were moderate-to-severe bronchopulmonary dysplasia,16.52% (113 of 671); severe intraventricular hemorrhage and/or periventricular leukomalacia, 2.49% (17 of 671); severe necrotizing enterocolitis, 2.63% (18 of 671); sepsis, 2.34% (16 of 671); and severe retinopathy of prematurity, 4.55% (27 of 593), 65.79% (450 of 671) survived without major morbidities. After adjustment for GA, birth weight, and 5-min Apgar score, antenatal steroid administration (OR = 2.397), antenatal magnesium sulfate administration (OR =  1.554) were the positivity factors to survival without major morbidity of VPIs, however, surfactant therapy (OR = 0.684,), and delivery room resuscitation (OR = 0.626) that were the negativity factors.ConclusionsThe present results indicate that survival and the incidence of survival without major morbidities increased with GA. Further, antenatal administration of steroids and magnesium sulfate, surfactant therapy, and delivery room resuscitation were pronounced determinants of survival without morbidities

FCGR3B*03 allele inheritance pattern in Brazilian families and some new variants of gene FCGR3B

BACKGROUND: the FCGR3B gene encoding the FcyRIIIb receptor for immunoglobulin G has three polymorphic forms known as HNA-1a, HNA-1b, and HNA-1c, encoded by the alleles FCGR3B*01, FCGR3B*02, and FCGR3B*03, respectively. It is not clear whether the inheritance of the FCGR3B*03 allele, which encodes the HNA-1c, is linked or not to the other two alleles. the objective of this study was to identify the inheritance pattern of the FCGR3B*03 allele in Brazilians.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, BR-04023902 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Reumatol, BR-04023902 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, BR-04023902 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Reumatol, BR-04023902 São Paulo, BrazilFAPESP: 05/55237-9Web of Scienc