Spontaneous Intraperitoneal Hemorrhage (SIPH): A New Differential Diagnosis for Complications Due to Protracted Vomiting.

Spontaneous intraperitoneal hemorrhage (SIPH), or abdominal apoplexy, is a rare complication of protracted vomiting. Although usually seen later in life, increased alcohol consumption may be contributory to the accelerated incidence of SIPH among younger populations. We describe a 22-year-old male who presented with abdominal pain after prolonged retching in the setting of binge drinking. A CT scan identified a highly attenuated intraperitoneal collection measuring 7.6 cm x 11.6 cm x 15.9 cm adjacent to the stomach. Due to hemodynamic instability, exploratory laparotomy was emergently performed and 1600 mL of blood was evacuated. A diagnosis of SIPH was made with bleeding visualized from a short gastric artery. Ultimately, vessel ligation failed to achieve hemostasis at the splenic hilum and a splenectomy was required. Given that a delay in identification may prove fatal, this case highlights the importance of recognizing SIPH as a differential diagnosis for unexplained abdominal pain and shock after persistent vomiting.

Enhanced contact hypersensitivity and antiviral immune responses in vivo by keratinocyte-targeted overexpression of IL-15.

IL-15 is involved in lymphocyte homeostasis. To investigate the role of IL-15 in the skin in vivo, mice were generated that overexpress IL-15 in keratinocytes, resulting in increased IL-15 protein levels in the skin but not elevated IL-15 serum concentrations. Keratin 14 (K14)-IL-15 transgenic (tg) mice showed increased contact hypersensitivity (CHS) responses. Transfer of primed wild-type (wt) and tg T cells into naive wt or tg recipients indicated that skin-derived IL-15 enhanced the induction but not the elicitation phase of CHS. Tg mice could be sensitized even by suboptimal hapten concentrations. Accordingly, Langerhans cells (LC) from tg skin were identified as potent allostimulators, suggesting the involvement of IL-15-stimulated LC in the induction of adaptive immunity. Overexpression of IL-15 also strengthened innate immunity since tg mice infected with human HSV type I developed significantly smaller HSV skin lesions. In addition, tg mice resisted re-infection with HSV more effectively than wt mice did, which was associated with an elevated anti-HSV Ab production. Accordingly, injection of serum from re-infected tg mice protected naive recipients significantly from epicutaneous HSV infection, indicating that anti-HSV Ab produced by tg mice play an important role in resistance in vivo. Together, our results show that overexpression of IL-15 in the epidermis enhances both innate and adaptive cutaneous immunity.

New views of the immunological synapse: variations in assembly and function.

The interaction of T cells with antigen-presenting cells results in the formation of a contact face, termed the immunological synapse. The prototypical dynamics of this process are well established and involve cessation of crawling, a highly fluid 'immature' synapse phase during which signaling is initiated, and ultimately the formation of a 'mature' synapse characterized by centralized and peripheral supramolecular activating complexes. Ongoing research is directed towards defining how these supramolecular assemblies are formed and, more importantly, to what end. With regard to the former, progress has been made in defining the order in which various molecules are recruited to signaling centers in prototypical settings. With regard to the latter, however, the issue now appears more complex, as both developmental changes in T cells and variations in the environment appear to modulate features of mature synapse development. Although many details of the immunological synapse have been established, emerging evidence suggests a great variability in the ultimate form of these contacts and their effects on T-cell functions.

CD28 signals in the immature immunological synapse.

T cell recognition of peptide-MHC complexes on APCs results in the aggregation of TCRs at a central supramolecular activation complex (c-SMAC) within a mature immunological synapse. T cells require a second "costimulatory" signal for activation, the most important of which, for naive T cells, is from CD28. However the time at which CD28-derived signals are induced relative to c-SMAC formation is not well understood. In this study, we have assessed the kinetics of CD28 localization and function relative to well-established aspects of c-SMAC formation. CD28 accumulates at the immature synapse alongside the TCR and is likewise enriched at the synapse at the onset of the calcium signal. In addition, using CD28 deficient or reconstituted murine cells in a single-cell recording approach shows that CD28 regulates this signal within seconds of a TCR-mediated rise in intracellular calcium levels. Finally, CD28 exerts effects on both the initiation and stabilization of the synapse in parallel with its effects on the downstream proliferation of T cells. Together, the data show that CD28 functions in the immunological synapse before the formation of the c-SMAC.

Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation.

CD28 costimulation is essential for CD4(+) T cell proliferation, survival, interleukin 2 (IL-2) production and T helper type 2 development. To define the nature of the signals that may drive different T cell responses, we have done a structure-function analysis of the CD28 cytoplasmic tail in primary T cells. CD28-mediated T cell proliferation and IL-2 production did not require a particular cytoplasmic domain. In contrast, IL-4 production was driven by the cooperative activity of specific motifs within the CD28 cytoplasmic tail. Using a gene-complementation approach, we provide evidence that one component of this T helper type 2 differentiation signal was mediated by 3-phosphoinositide-dependent protein kinase 1. Thus, different mechanisms underlie the induction of distinct T cell functional responses by CD28.