The CD2-CD58 recognition system promotes adhesion and signaling and counters exhaustion in human T cells. We found that CD2 localized to the outer edge of the mature immunological synapse (IS), with cellular or artificial APC, in a pattern we refer to as a "CD2 corolla". The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 costimulators. The corolla amplified active phosphorylated Src-family kinases (pSFK), LAT and PLC-γ over T cell receptor (TCR) alone. CD2-CD58 interactions in the corolla boosted signaling by 77% compared to central CD2-CD58 interactions. Engaged PD-1 invaded the CD2 corolla and buffered CD2 mediated amplification of TCR signaling. CD2 numbers and motifs in its cytoplasmic tail controlled corolla formation. CD8 + tumor infiltrating lymphocytes displayed low expression of CD2 in the majority of colorectal, endometrial and ovarian cancer patients. CD2 down-regulation may attenuate anti-tumor T cell responses with implications for checkpoint immunotherapies.
A patient who abused nitrous oxide chronically developed ataxia, paresthesia, and urinary retention while self-medicating with cyanocobalamin. A diagnosis of SCD was supported by MRI findings, symptoms, and the known relationship between nitrous oxide exposure and vitamin B12 deficiency.
There is a lack of a neuroimaging biomarker for HIV-Associated Neurocognitive Disorder. We report magnetoencephalography (MEG) data from patients with HIV disease and risk-group appropriate controls that were collected to determine the MEG frequency profile during the resting state, and the stability of the profile over 24 weeks. 17 individuals (10 HIV+, 7 HIV−) completed detailed neurobehavioral evaluations and 10 minutes of resting-state MEG acquisition with a 306-channel whole-head system. The entire evaluation and MEG measurement were repeated 24 weeks later. Relative MEG power in the delta (0–4 Hz), theta (4–7 Hz), alpha (8–12 Hz), beta (12–30 Hz) and low gamma (30–50 Hz) bands was computed for 8 predefined sensor groups. The median stability of resting-state relative power over 24 weeks of follow-up was 0.80 with eyes closed, and 0.72 with eyes open. The relative gamma power in the right occipital (t(15) = 1.99, p < .06, r = −.46) and right frontal (t(15t) = 2.15, p < .05, r = −.48) regions was associated with serostatus. The effect of age on delta power was greater in the seropositive subjects (r2 = .51) than in the seronegative subjects (r2 = .11). Individuals with high theta-to-gamma ratios tended to have lower cognitive test performance, regardless of serostatus. The stability of the wide-band MEG frequency profiles over 24 weeks supports the utility of MEG as a biomarker. The links between the MEG profile, serostatus, and cognition suggest further research on its potential in HAND is needed.
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