TCR-Vγδ usage distinguishes protumor from antitumor intestinal γδ T cell subsets.

γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but they also constitute a major lymphocyte population infiltrating colorectal cancers (CRCs); however, their temporal contribution to CRC development or progression remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in premalignant or nontumor colons exhibit cytotoxic markers, whereas tumor-infiltrating γδ T cells express a protumorigenic profile. These contrasting T cell profiles were associated with distinct T cell receptor (TCR)-Vγδ gene usage in both humans and mice. Longitudinal intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, whereas targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover temporal pro- and antitumor roles for γδ T cell subsets.

Acute Pancreatitis after Colonoscopy: A Case Presentation and Literature Review.

We report a case of acute pancreatitis after an elective screening colonoscopy. A 51-year-old male with a left ventricular assist device for end-stage nonischemic cardiomyopathy and a family history of colorectal cancer was admitted for an expedited heart transplant evaluation. He underwent screening colonoscopy during this admission which was technically uncomplicated apart from requiring slight maneuvering at the splenic flexure. The following day, the patient developed acute epigastric pain and one episode of emesis. Subsequent laboratory evaluation revealed a significantly elevated lipase level and cross-sectional imaging consistent with acute pancreatitis. With no evidence of gallstones, alcohol use, and hypertriglyceridemia, the acute pancreatitis was deemed to be a complication of colonoscopy. The presumed mechanism of the pancreatitis was due to mechanical trauma from insufflation and abdominal pressure, applied to at the splenic flexure, which is in close proximity to the pancreatic tail. The patient was treated with supportive care (intravenous fluid, analgesia, and pancreatic rest) and improved significantly over a three-day period.

In vitro restoration of Th17 response during HIV infection with an antiretroviral drug and Th17 differentiation cytokines.

The Th17 subset is preferentially depleted as compared to the Th1 subset in chronically HIV-infected patients, even after successful antiretroviral therapy. In this study, we have established an in vitro system utilizing primary human CD4 T cell cultures that recapitulates the dramatic loss of Th17 response upon HIV-1 infection that is accompanied with a less profound Th1 decrease. With this experimental system, we showed that blocking viral entry with CCR5 ligands or TAK779 reduced the infection and enhanced Th17 response but not Th1 response. Antiretroviral drug 3TC (lamivudine), given at the time of infection, completely prevented the loss of Th17 and Th1 responses but was ineffective when given after infection was already established. Only when Th17 differentiation cytokines were given along with 3TC to the cultures with established HIV infection was Th17 response fully restored and virus replication kept suppressed. Finally, a significant increase of Th17 response was achieved in peripheral lymphocytes of HIV-infected patients on antiretroviral therapy after treatment with Th17 differentiation cytokines. These data demonstrate the presence of CD4 T cells remaining capable of mounting Th17 response during HIV infection and indicate the potential use of immunotherapeutic modalities to supplement antiretroviral drugs for restoring Th17 response in chronically HIV-infected patients.

The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (FcgammaRIIa) mediated signaling.

To achieve an adequate response, cells of the immune system must be tightly regulated to avoid hypo or hyper responsiveness. One of the mechanisms used by the immune system to avoid excessive inflammation is the modulation of the response through inhibitory receptors containing immunoreceptor tyrosine based inhibitory motifs (ITIM). Here, we show that human neutrophils from peripheral blood express the ITIM containing CD300a (also known as IRp60 and CMRF-35H) receptor. By using the HL-60 differentiation model, we show that the expression of CD300a receptor is developmentally regulated. Stimulation of human neutrophils with LPS and GM-CSF increased the cell surface expression of CD300a as a result of the rapid translocation of an intracellular pool of the receptor to the cell surface. Co-ligation of CD300a with the immunoreceptor tyrosine based activating motif (ITAM) containing CD32a (FcgammaRIIa) activation receptor inhibited CD32a mediated signalling; whereas, it did not inhibit toll-like receptor (TLR)-4 mediated reactive oxygen species (ROS) production. Therefore, at least for human neutrophils, the inhibitory signals mediated by the CD300a receptor may be selective in their action.