Anti-THY1 monoclonal antibody, clone OX-7

Intraepithelial lymphocytes (IELs) are resident cells localized within the intestinal epithelia and play an important role in regulating gut inflammations and host defense against pathogens. CD8 alpha(+) TCR alpha beta(+) IELs are heterogeneous populations that are generated from T cell precursors including CD4(-) CD8 alpha(-) double-negative (DN) cells and CD4(+) CD8 alpha(+) double-positive (DP) cells. However, developmental pathways of TCR alpha beta(+) IELs remained unclear. To gain insight into the mechanisms, we generated mice (Bcl11b(Delta DN2) mice) that lack thymic precursors (DN CD5(+) TCR beta(+) cells) for CD4(-) CD8 alpha alpha(+) TCR alpha beta(+) IELs. Unexpectedly, we found that, in the absence of the precursors in thymi of Bcl11b(Delta DN2) mice, CD4(-) CD8 alpha alpha(+) TCR alpha beta(+) IELs were still present in the intestine though the number was reduced. Adoptive transfer experiment showed that their precursors were highly enriched in CD8 alpha(+) TCR beta(-) thymocytes. The CD4(-) CD8 alpha alpha(+) TCR alpha beta(+) IELs in Bcl11b(Delta DN2) mice are distinguished by Thy1.2 expression and are indeed present in WT mice. Taken together, our study reveal a novel developmental pathway for CD8 alpha alpha(+) TCR alpha beta(+) IELs.

Traumatic brain injury (TBI) research has focused on moderate to severe injuries as their outcomes are significantly worse than those of a mild TBI (mTBI). However, recent epidemiological evidence has indicated that a series of even mild TBIs greatly increases the risk of neurodegenerative and psychiatric disorders. Neuropathological studies of repeated TBI have identified changes in neuronal ionic concentrations, axonal injury, and cytoskeletal damage as important determinants of later life neurological and mood compromise; yet, there is a paucity of data on the contribution of neurogliovascular dysfunction to the progression of repeated TBI and alterations of brain function in the intervening period. Methods: Here, we established a mouse model of repeated TBI induced via three electromagnetically actuated impacts delivered to the intact skull at three-day intervals and determined the long-term deficits in neurogliovascular functioning in Thy1-ChR2 mice. Two weeks post the third impact, cerebral blood flow and cerebrovascular reactivity were measured with arterial spin labelling magnetic resonance imaging. Neuronal function was investigated through bilateral intracranial electrophysiological responses to optogenetic photostimulation. Vascular density of the site of impacts was measured with in vivo two photon fluorescence microscopy. Pathological analysis of neuronal survival and astrogliosis was performed via NeuN and GFAP immunofluorescence. Results: Cerebral blood flow and cerebrovascular reactivity were decreased by 50 +/- 16% and 70 +/- 20%, respectively, in the TBI cohort relative to sham-treated animals. Concomitantly, electrophysiological recordings revealed a 97 +/- 1% attenuation in peri-contusional neuronal reactivity relative to sham. Peri-contusional vascular volume was increased by 33 +/- 2% relative to sham-treated mice. Pathological analysis of the peri-contusional cortex demonstrated astrogliosis, but no changes in neuronal survival. Conclusion: This work provides the first in-situ characterization of the long-term deficits of the neurogliovascular unit following repeated TBI. The findings will help guide the development of diagnostic markers as well as therapeutics targeting neurogliovascular dysfunction.