Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues

PD-1 is a member of the immunoglobulin superfamily expressed on immune cells, including T and B cells, and is involved in the delivery of inhibitory signal upon engagement of its ligands, PD-L1 and PD-L2. While the expression profile of PD-1 has been well documented, the analysis of PD-L1 and PD-L2 distributions on a protein basis has not been carried out because of the lack of available monoclonal antibodies specific for the molecules. In this study, we established two monoclonal antibodies, 1-111A and 122, specific for murine PD-L1 and PD-L2, respectively, and examined their expression profiles. Based on flow cytometric analyses, the expression of PD-L1 was detected in a variety of lymphohematopoietic cell types, including a minor proportion of T and B cells in the spleen, majority of pre-B cells and myeloid cells in bone marrow and subsets of thymocytes, while the expression of PD-L2 was not observed in the lymphohematopoietic cells at all. Notably, a significant proportion of the most immature lineage-marker-negative and c-Kit-positive bone marrow cells containing stem cells did express PD-L1. Following mitogenic stimulation, essentially all lymphocytes expressed PD-L1. Furthermore, a variety of leukemic lines also expressed PD-L1, while none of them did PD-L2. Thus, present results demonstrate the distinct expression patterns of PD-L1 and PD-L2 with the cells of lymphohematopoietic tissues exclusively expressing the former.     

The Long Elusive IgM Fc Receptor,FcμR

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune “natural” and antigen-induced “immune” IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcμR). We have recently identified a bona fide FcμR in both humans and mice. In this article we briefly review what we have learned so far about FcμR.     

Requirement of high-affinity IL-2-IL-2R interaction for T cell anergy induction

Incomplete T cell antigen receptor-mediated signaling induces an unresponsive state known as anergy. Previously, we had shown that anergy can be induced in antigen-primed but not naive T cells. In this report, we found that in vitro primed T cells from IL-2R alpha-deficient mice were resistant to anergy induction in contrast to comparably treated wild-type T cells. This resistance persisted even after proliferation of IL-2R alpha chain-deficient CD4 T cells with high-dose IL-2-IL-2R beta gamma chains interaction. Thus, antigen activation, and/or progression through cell cycle are not sufficient to induce anergy susceptibility in T cells. The high-affinity IL-2-IL-2R interaction appears to play a critical role in this process.     

Benign osteoblastoma of the temporal bone.

We report a case of benign osteoblastoma arising in the temporal bone of a 28-year-old woman. Plain radiography showed a mass with an amorphous calcified matrix and a thin radiolucent marginal zone. CT and MR imaging were useful in delineating the extent of the tumor, and angiography showed its hypervascularity. Preoperative transarterial embolization was effective in reducing bleeding during surgery.     

Cloning of mouse immunoglobulin epsilon gene and its location within the heavy chain gene cluster.

Mouse immunoglobulin epsilon chain gene was cloned from DNA of a hybridoma producing anti-dinitrophenyl IgE, which was constructed by fusing a spleen cell of a BALB/c mouse with a variant clone of MOPC21 myeloma (IgG1 producer). Because a given active heavy chain constant region (CH) gene is linked to a heavy chain joining segment (JH) gene at its 5' side, the expressed C epsilon gene of the hybridoma was cloned from a phage library containing partial Sau3A digests of IgE hybridoma DNA by using a J gene fragment as a probe. Among 6 X 10(5) phages screened, five positive clones were obtained and three of them were identified as C epsilon gene clones by restriction mapping, Southern blot hybridization, R-loop formation, and partial nucleotide sequence determination. The determined nucleotide sequence predicted the amino acid sequence which resembles a part of the CH3 domain of human epsilon chain. The deletion profile of the C epsilon gene in various myelomas expressing different CH genes indicates that the C epsilon gene is located between the C gamma 2a and C alpha genes. The linkage (5'-epsilon-alpha-3') was directly confirmed by molecular cloning of the overlapping chromosomal segments from newborn mouse DNA.     

Prediction of infarct volume and neurologic outcome by using automated multiparametric perfusion-weighted magnetic resonance imaging in a primate model of permanent middle cerebral artery occlusion

By optimizing thresholds, we identified the perfusion-weighted magnetic resonance imaging (PWI) parameters that accurately predict final infarct volume and neurologic outcome in a primate model of permanent middle cerebral artery (MCA) occlusion. Ten cynomolgus monkeys underwent PWI and diffusion-weighted imaging (DWI) at 3 and 47 hours, respectively, after right MCA occlusion using platinum coils, and were killed at 48 hours. Volumes of the hypoperfused areas on PWI were automatically measured using different thresholds and 11 parametric maps to determine the optimum threshold (at which least difference was found between the average volumes on PWI and those determined using specimens or DWI). In the case of arrival time (AT), cerebral blood volume (CBV), time to peak (TTP), time to maximum (T_max), and cerebral blood flow (CBF) determined using deconvolution techniques, the volume of the hypoperfused area significantly correlated with the infarct volumes and the neurologic deficit scores with small variations, whereas in the case of mean transit time and nondeconvolution CBF, relatively poor correlations with large variations were seen. At optimum threshold, AT, CBV, TTP, T_max, and deconvolution CBF can accurately predict the final infarct volume and neurologic outcome in monkeys with permanent MCA occlusion.     

Pressure between the humeral head and the subscapularis tendon after the modified Boytchev procedure

The pressure between the humeral head and the subscapularis tendon was determined in 32 patients who had recurrent anterior shoulder dislocations. These patients' pressures were measured during a modified Boytchev procedure both before and after transposition of the conjoined tendon, and they were remeasured at the time of screw removal, performed at a mean of 13 months after the initial surgery. The mean clinical follow-up period was 31 months. A micro-tip catheter transducer was inserted into the glenohumeral joint between the humeral head and the subscapularis tendon. Pressures were measured at particular degrees of motion for two positions: passive external rotation of the arm at the side at 0 degrees, 15 degrees, 30 degrees, 45 degrees, and 60 degrees and passive external rotation at the 90 degrees abducted position at 0 degrees, 30 degrees, 60 degrees, and 90 degrees. The pressures were statistically significantly higher after the conjoined tendon transfer at all measured degrees of motion in the two positions. The pressures at the time of screw removal were not statistically significantly different from those seen after the tendon transfer during external rotation at 90 degrees of abduction. The modified Boytchev procedure increases the pressure between the humeral head and the subscapularis tendon. We suspect that this increased pressure increases proprioceptive stimuli in the subscapularis tendon and thus accelerates the protective reflex needed to prevent shoulder dislocation.     

Hypothalamic hamartoma associated with anterior paraclinoid aneurysm of the internal carotid artery

A 15-year-old boy presented with a history of medically refractory gelastic seizures and cognitive impairments. Neuroimaging demonstrated a sessile type hypothalamic hamartoma, which was treated by gamma knife surgery. However, the gelastic seizures only partially decreased and the frequency of seizures remained unchanged. One year later, angiography before surgery detected anterior paraclinoid aneurysm of the left internal carotid artery. Blood pressure and endocrinological examinations showed no abnormality. Direct surgery was performed to treat the aneurysm and hamartoma. No sclerotic changes were noted in the arterial wall. The aneurysm was treated with clipping, and the hamartoma was partially removed. Postoperative course was uneventful and the gelastic seizures disappeared. No evidence for a causal relationship between the hamartoma and aneurysm was found.