Dysregulated CD4 T cell responses are causally linked to autoimmune and chronic inflammatory disorders, yet the cellular attributes responsible for maintaining the disease remain poorly understood. Herein, we identify a discrete population of effector CD4 T cells that is able to both sustain and confer intestinal inflammation. This subset of pathogenic CD4 T cells possesses a unique gene signature consistent with self-renewing T cells and hematopoietic progenitor cells, exhibits enhanced survival, and continually seeds the terminally differentiated IFNγ-producing cells in the inflamed intestine. Mechanistically, this population selectively expresses the glycosyltransferase ST6Gal-I, which is required for optimal expression of the stemness-associated molecule TCF1 by effector CD4 T cells. Our findings indicate that the chronicity of T cell-mediated inflammation is perpetuated by specific effector CD4 T cells with stem-like properties.
Effector and memory CD4 and CD8 T cell responses are critical for the control of many intracellular pathogens. The development of these populations is governed by transcription factors that molecularly control their differentiation, function, and maintenance. Two transcription factors known to be involved in these processes are Tbet and STAT4. Although Tbet has been shown to regulate CD8 T cell fate decisions and effector CD4 T cell choices, the contribution of STAT4 is less well understood. To address this, we examined the impact of STAT4 on T cell responses in the presence or absence of Tbet, following LCMV infection by using mice lacking Tbet, STAT4, or both transcription factors. STAT4 was not required for Tbet or Eomes expression; however, virus-specific effector CD8 T cells are skewed toward a memory-precursor phenotype in the absence of STAT4. This altered proportion of memory precursors did not result in an increase in memory CD8 T cells after the resolution of the infection. We also demonstrate that virus-specific effector and memory CD4 T cells formed independently of Tbet and STAT4, although a slight reduction in the number of antigen-specific CD4 T cells was apparent in mice lacking both transcription factors. Collectively, we have discovered distinct roles for Tbet and STAT4 in shaping the phenotype and function of virus-specific T cell responses.
BACKGROUND Anastomotic leak (AL) after low anterior resection (LAR) can be a highly morbid complication. The incidence of AL ranges from 5% to 20% depending on patient characteristics and the distance of the anastomosis from the anal verge. Low anastomoses and leaks pose technical challenges for endoscopic treatment. The aim of this report was to describe the use of a commercially available laparoscopic energy device through a transanal minimally invasive surgery (TAMIS) port for the management of a symptomatic leak not requiring relaparotomy (grade B) after a LAR with diverting loop ileostomy. CASE SUMMARY A TAMIS GelPOINT Path port was inserted into the anus to access the distal rectum. Pneumorectum was achieved with AirSeal insufflation and a 30 degree laparoscope was introduced through a trocar. A LigaSure TM Retractable L-Hook device was then used to perform a septotomy of the chronic sinus tract identified posterior to the coloproctostomy. The procedure was then repeated twice in three weeks intervals with ultimate resolution of the chronic leak cavity. Several months after serial TAMIS septotomies, barium enema demonstrated a patent anastomosis with no evidence of persistent leak or stricture. The patient subsequently underwent ileostomy reversal and has had no significant post-operative issues. CONCLUSION TAMIS septotomy with the LigaSure TM Retractable L-Hook is a feasible and effective, minimally invasive salvage technique for the treatment of grade B ALs. Larger studies are needed to assess the generalizability and long-term results of this technique.
BackgroundChest wall sarcomas are a rare group of soft tissue malignancies with variable presentations. Here we describe the definitive management of a large, rapidly progressing chest wall sarcoma arising from the pectoralis major muscle.Case reportAn obese 42-year-old African American male with multiple medical comorbidities presented with new onset right-sided chest pain and a palpable right chest mass. Initial CT chest demonstrated a 9x9x9cm necrotic mass arising from the pectoralis major. CT-guided core biopsy was positive for high-grade spindle cell neoplasm (positive for smooth muscle actin, desmin, S100, and CD31; negative for CD34, PAX8, and beta-catenin). Staging imaging 2 months later demonstrated growth of the mass to 21.4 × 17.8 × 13.7 cm. The patient underwent neoadjuvant chemoradiation with surveillance CT imaging demonstrating a stable tumor. Then he underwent wide local excision of the mass followed by delayed local myocutaneous flap reconstruction and skin grafting. Final pathology was R0 resection, 38x20x18 cm tumor with 70% gross necrosis. Microscopic examination confirmed high-grade sarcoma with smooth muscle differentiation. Final pathologic staging was Stage III G3 pT2bNxMx.ConclusionsThis patient presented with a rare, rapidly enlarging high-grade leiomyosarcoma of the chest wall without metastases or violation of the thorax. We describe the definitive management including a multidisciplinary team to manage a complex and rapidly progressive sarcoma of the chest wall.
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