ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS.
ICOS信号转导在用疟原虫chabaudi chabaudi AS重新攻击后促进继发性体液反应。
- 作者列表："Latham LE","Wikenheiser DJ","Stumhofer JS
:The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is largely unexplored. Here we show that memory T cell formation and maintenance are influenced by persistent infection with P. chabaudi chabaudi AS infection, as memory T cell numbers decline in wild-type and Icos-/- mice after drug-clearance. Following drug-clearance Icos-/- mice display a relapsing parasitemia that occurs more frequently and with higher peaks compared to wild-type mice after re-challenge. The secondary immune response in Icos-/- mice is characterized by significant impairment in the expansion of effector cells with a Tfh-like phenotype, which is associated with a diminished and delayed parasite-specific Ab response and the absence of germinal centers. Similarly, the administration of an anti-ICOSL antagonizing antibody to wild-type mice before and after reinfection with P. c. chabaudi AS leads to an early defect in Tfh cell expansion and parasite-specific antibody production, confirming a need for ICOS-ICOSL interactions to promote memory B cell responses. Furthermore, adoptive transfer of central memory T (TCM) cells from wild-type and Icos-/- mice into tcrb-/- mice to directly evaluate the ability of TCM cells to give rise to Tfh cells revealed that TCM cells from wild-type mice acquire a mixed Th1- and Tfh-like phenotype after P. c. chabaudi AS infection. While TCM cells from Icos-/- mice expand and display markers of activation to a similar degree as their WT counterparts, they displayed a reduced capacity to upregulate markers indicative of a Tfh cell phenotype, resulting in a diminished humoral response. Together these findings verify that ICOS signaling in memory T cells plays an integral role in promoting T cell effector responses during secondary infection with P. c. chabaudi AS.
: 共刺激分子ICOS与T辅助细胞应答的诱导和调节相关，包括滤泡辅助T (Tfh) 细胞的分化以及记忆T细胞的形成和维持。然而，ICOS信号传导在次级免疫应答中的作用在很大程度上尚未探索。在这里，我们表明记忆T细胞的形成和维持受到感染P. chabaudi chabaudi的持续感染的影响，因为药物清除后野生型和Icos-/-小鼠的记忆T细胞数量下降。药物清除后，Icos-/-小鼠显示出复发的寄生虫血症，与再攻击后的野生型小鼠相比，其发生更频繁且具有更高的峰。Icos-/-小鼠中的次级免疫应答的特征在于具有Tfh样表型的效应细胞的扩增的显著损害，这与减少和延迟的寄生虫特异性Ab应答以及不存在生发中心有关。同样，在用P. c. chabaudi AS再感染之前和之后，给予野生型小鼠抗ICOSL拮抗抗体导致Tfh细胞扩增和寄生虫特异性抗体产生的早期缺陷，证实需要ICOS-ICOSL相互作用来促进记忆b细胞反应。此外，中枢记忆T (TCM) 的过继转移来自野生型和Icos-/-小鼠的细胞进入tcrb-/-小鼠以直接评估TCM细胞产生Tfh细胞的能力，揭示了来自野生型小鼠的TCM细胞在P后获得了混合的Th1和Tfh样表型。c. chabaudi作为感染。虽然来自Icos-/-小鼠的TCM细胞扩增并显示活化标志物至与其WT对应物相似的程度，但它们显示上调指示Tfh细胞表型的标志物的能力降低，导致体液反应减弱。这些发现一起验证了记忆T细胞中的ICOS信号在P. c. chabaudi AS的二次感染期间促进T细胞效应应答中起着不可或缺的作用。
METHODS::More than 10 years after the Centers for Disease Control and Prevention recommended routine HIV testing for patients in emergency departments (ED) and other clinical settings, as many as three out of four patients may not be offered testing, and those who are offered testing frequently decline. The current study examines how participant characteristics, including demographics and reported substance use, influence the efficacy of a video-based intervention designed to increase HIV testing among ED patients who initially declined tests offered by hospital staff. Data from three separate trials in a high volume New York City ED were merged to determine whether patients (N = 560) were more likely to test post-intervention if: (1) they resembled people who appeared onscreen in terms of gender or race; or (2) they reported problem substance use. Chi Square and logistic regression analyses indicated demographic concordance did not significantly increase likelihood of accepting an HIV test. However, participants who reported problem substance use (n = 231) were significantly more likely to test for HIV in comparison to participants who reported either no problem substance use (n = 190) or no substance use at all (n = 125) (x2 = 6.830, p < 0.05). Specifically, 36.4% of patients who reported problem substance use tested for HIV post-intervention compared to 30.5% of patients who did not report problem substance use and 28.8% of participants who did not report substance use at all. This may be an important finding because substance use, including heavy alcohol or cannabis use, can lead to behaviors that increase HIV risk, such as sex with multiple partners or decreased condom use.
METHODS::HIV self-testing has the potential to improve test access and uptake, but concerns remain regarding counselling and support during and after HIV self-testing. We investigated an oral HIV self-testing strategy together with a mobile phone/tablet application to see if and how it provided counselling and support, and how it might impact test access. This ethnographic study was nested within an ongoing observational cohort study in Cape Town, South Africa. Qualitative data was collected from study participants and study staff using 33 semi-structured interviews, one focus group discussion, and observation notes. The app provided information and guidance while also addressing privacy concerns. The flexibility and support provided by the strategy gave participants more control in choosing whom they included during testing. Accessibility concerns included smartphone access and usability issues for older and rural users. The adaptable access and support of this strategy could aid in expanding test access in South Africa.
METHODS:BACKGROUND:Several Kell-system antibodies are known to cause direct agglutination. Also, some specificities, such as anti-Ku, have been reported to react only via the indirect antiglobulin test (IAT). METHODS:Herein, we describe the case of a 61-year-old alloimmunized white woman who presented to an outside hospital with a gastrointestinal (GI) bleed and a "possible anti-Ku" was reported with 3+ reactivity at PEG-IAT and at Ficin-IAT; in addition to an unidentified cold antibody. Subsequently, when the patient presented to a second outside hospital, an anti-Ku that caused 3+ to 4+ reactions at saline-immediate spin (IS) was identified. The reactivity was evaluated with 0.01-M dithiothreitol (DTT) treatment of the plasma. RESULTS:It was determined that the strong agglutination with saline-IS was caused by immunoglobulin (Ig)M anti-Ku. CONCLUSION:To our knowledge, this is the first reported case of an IgM anti-Ku.