Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.     

The final destiny of acantholytic cells in pemphigus is Fas mediated

Background  Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective  This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods  Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results  All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4⁺CD69⁺ cells. Additionally, CD19⁺ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion  This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

Conflicts of interest

None declared.     

Nuclear RNA sequences coding for alpha and beta globins in erythroid cells: evidence for multiple intermediate molecules

The poly (A)-containing nuclear RNA from dimethylsulfoxide-induced Friend leukemia cells was fractionated by acrylamide gel electrophoresis in denaturing conditions and analyzed for alpha and beta globin RNA sequences. The results indicate that nuclear RNA contains one species of large-size RNA (0.6 X 10(6) daltons), which is the putative precursor for beta globin mRNA only. In addition, it was shown by electrophoretic analysis that the complex of RNA molecules not resolved by sucrose gradient centrifugation (11S) comprises sequences of decreasing size (0.34, 0.28, and 0.26 X 10(6) daltons), which might be the precursors of alpha and beta globin mRNA.     

Cytomegalovirus vector expressing RAE‐1γ induces enhanced anti‐tumor capacity of murine CD8+ T cells

Designing CD8⁺ T‐cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE‐1γ as CD8⁺ T cell‐based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE‐1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD‐1. CMV vector expressing RAE‐1γ potentiated expansion of KLRG1⁺ CD8⁺ T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long‐term maintenance of epitope‐specific CD8⁺ T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8⁺ T‐cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8⁺ T‐cell sensitive tumors.