To fully perform their functions, T lymphocytes migrate within organs' parenchyma and interact with local cells. Infiltration of T lymphocytes within the central nervous system (CNS) is associated ...with numerous neurodegenerative disorders. Nevertheless, how these immune cells communicate and respond to neural cells remains unresolved. To investigate the behavior of T lymphocytes that reach the CNS, we have established an
co-culture model and analyzed the spatiotemporal interactions between human activated CD8
T lymphocytes and primary human astrocytes and neurons using time-lapse microscopy. By combining multiple variables extracted from individual CD8
T cell tracking, we show that CD8
T lymphocytes adopt a more motile and exploratory behavior upon interacting with astrocytes than with neurons. Pretreatment of astrocytes or neurons with IL-1β to mimic
inflammation significantly increases CD8
T lymphocyte motility. Using visual interpretation and analysis of numerical variables extracted from CD8
T cell tracking, we identified four distinct CD8
T lymphocyte behaviors: scanning, dancing, poking and round. IL-1β-pretreatment significantly increases the proportion of scanning CD8
T lymphocytes, which are characterized by active exploration, and reduces the proportion of round CD8
T lymphocytes, which are less active. Blocking MHC class I on astrocytes significantly diminishes the proportion of poking CD8
T lymphocytes, which exhibit synapse-like interactions. Lastly, our co-culture time-lapse model is easily adaptable and sufficiently sensitive and powerful to characterize and quantify spatiotemporal interactions between human T lymphocytes and primary human cells in different conditions while preserving viability of fragile cells such as neurons and astrocytes.
We report a case of subdural empyema in a homeless patient caused by Bartonella quintana. B. quintana is a facultative intracellular bacteria for which bacterial growth is fastidious. The molecular ...biology approach has been a real help in establishing the diagnosis.
A 59-years old homeless patient, with a history of chronic alcohol abuse, was brought to the emergency department with a massive subdural empyema. Extensive microbiological evaluation didn't reveal any pathogen in the pus collected before antibiotic treatment. B. quintana was detected in the pus from the empyema using a 16S rRNA-based PCR. Histology of intraoperative samples was consistent with the diagnosis and a serological assay was positive. The patient responded well to a treatment that included craniectomy with drainage of the loculated pus, total removal of the infected capsule and a combination of antibiotics.
This unique case of B. quintana-related empyema illustrates the risk of secondary infection of subdural hematoma with B. quintana since such infections have recently reemerged, predominantly among the homeless populations. Patients with subdural empyema in at-risk populations should be systematically evaluated for B. quintana with an appropriate diagnostic approach involving molecular biology.
Cancer immunotherapy using genetically modified immune cells such as those expressing chimeric antigen receptors has shown dramatic outcomes in patients with refractory and relapsed malignancies. ...Natural killer (NK) cells as a member of the innate immune system, possessing both anticancer (cytotoxic) and proinflammatory (cytokine) responses to cancers and rare off-target toxicities have great potential for a wide range of cancer therapeutic settings. Therefore, improving NK cell antitumor activity through genetic modification is of high interest in the field of cancer immunotherapy. However, gene manipulation in primary NK cells has been challenging because of broad resistance to many genetic modification methods that work well in T cells. Here we review recent successful approaches for genetic and epigenetic modification of NK cells including epigenetic remodeling, transposons, mRNA-mediated gene delivery, lentiviruses, and CRISPR gene targeting.
Brucellosis is a zoonotic disease located especially in Central and South America, India, the Mediterranean and the Middle East. Human brucellosis occurs as a systemic infectious disease with various ...clinical manifestations. We present a case of 45-year-old female patient, nulliparous, not sexually active, with a previous medical history of a treated brucellosis, and no surgical or gynecological history. The patient presented with a history of fever for 7 days of 39 degrees Celsius, chills and acute abdominal pain. She was diagnosed with diffuse peritonitis with left tubo-ovarian abscess and was admitted for an urgent diagnostic laparoscopy. A left adnexectomy was performed. The diagnosis of genital brucellosis was made. This case report discusses an unusual complication of brucellosis represented by a tubo-ovarian abscess associated with acute peritonitis, treated by a laparoscopic adnexectomy and antimicrobials. Acute peritonitis associated with a tubo-ovarian abscess is an unusual complication of brucellosis.
The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PIDs), including severe ...combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PIDs in multicenter longitudinal retrospective, prospective, and cross-sectional studies. Since 2009, participating centers have enrolled more than 800 subjects on PIDTC protocols for SCID, and enrollment in the studies on WAS and CGD is underway. Four pilot projects have been funded, and 12 junior investigators have received fellowship awards. Important publications of the consortium describe the outcomes of hematopoietic cell transplantation for SCID during 2000-2009, diagnostic criteria for SCID, and the pilot project of newborn screening for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups, and international colleagues. Funded by the National Institute of Allergy and Infectious Diseases and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, the PIDTC has recently received renewal for another 5 years. Here we review accomplishments of the group, projects underway, highlights of recent workshops, and challenges for the future.
Summary
Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized ...that IR‐induced senescence markers could persist long‐term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16INK4a expression, two hallmarks of cellular senescence and aging. BrdU‐labeling experiments revealed that IR‐induced damaged cells are preferentially eliminated, at least partially, in a tissue‐dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild‐type and Rag2−/− γC−/− mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long‐term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.
Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The ...most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS).
(
, present on chromosome 22, is responsible for thymic epithelial development. Single variants in
causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to
haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections.
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