The Case to Preserve Criminal Jurisdiction Immunity Accorded Foreign Diplomatic and Consular Personnel in the United States

Recently proposed federal legislation would remove criminal jurisdiction immunity presently enjoyed as a matter of right by foreign diplomatic and consular personnel residing in the United States. Such legislation reflects, in the authors\u27 views, both a misplaced concern, expressed in the media and in the recent legal literature, about the threat posed to American society by diplomatic crime, and a misunderstanding of existing international and domestic law on diplomatic privileges and immunities. The authors oppose any alteration of the present law on grounds that it is unwarranted on the facts, that it would contravene international and domestic law, that it would be inconsistent with the foundational theories underlying criminal jurisdiction immunity, and that it would unnecessarily expose the United States diplomatic corps serving abroad to reciprocal, retaliatory action by other nations. The authors argue that the present law, if vigorously pursued when appropriate, affords ample deterrence and adequate remedies. The authors also reject suggestions to mandate any insurance schemes or compensation funds for victims of diplomatic crime on grounds that this is a matter better addressed through informal negotiation conducted on a case by case basis by the State Department with the foreign mission of the offender

Maladaptive lymphangiogenesis is associated with synovial iron accumulation and delayed clearance in factor VIII–deficient mice after induced hemarthrosis

BackgroundMechanisms of iron clearance from hemophilic joints are unknown.ObjectivesTo better understand mechanisms of iron clearance following joint bleeding in a mouse model of hemophilia.MethodsHemarthrosis was induced by subpatellar puncture in factor VIII (FVIII)-deficient (FVII-/-) mice, +/- periprocedural recombinant human FVIII, and hypocoagulable (HypoBALB/c) mice. HypoBALB/c mice experienced transient FVIII deficiency (anti-FVIII antibody) at the time of injury combined with warfarin-induced hypocoagulability. Synovial tissue was harvested weekly up to 6 weeks after injury for histological analysis, ferric iron and macrophage accumulation (CD68), blood and lymphatic vessel remodeling (αSMA; LYVE1). Synovial RNA sequencing was performed for FVIII-/- mice at days 0, 3, and 14 after injury to quantify expression changes of iron regulators and lymphatic markers.ResultsBleed volumes were similar in FVIII-/- and HypoBALB/c mice. However, pronounced and prolonged synovial iron accumulation colocalizing with macrophages and impaired lymphangiogenesis were detected only in FVIII-/- mice and were prevented by periprocedural FVIII. Gene expression changes involved in iron handling (some genes with dual roles in inflammation) and lymphatic markers supported proinflammatory milieu with iron retention and disturbed lymphangiogenesis.ConclusionAccumulation and delayed clearance of iron-laden macrophages were associated with defective lymphangiogenesis after hemarthrosis in FVIII-/- mice. The absence of such findings in HypoBALB/c mice suggests that intact lymphatics are required for removal of iron-laden macrophages and that these processes depend on FVIII availability. Studies to elucidate the biological mechanisms of disturbed lymphangiogenesis in hemophilia appear critical to develop new therapeutic targets

A variant of SCID with specific immune responses and predominance of γδ T cells

We describe here a patient with a clinical and molecular diagnosis of recombinase activating gene 1–deficient (RAG1-deficient) SCID, who produced specific antibodies despite minimal B cell numbers. Memory B cells were detected and antibodies were produced not only against some vaccines and infections, but also against autoantigens. The patient had severely reduced levels of oligoclonal T cells expressing the αβ TCR but surprisingly normal numbers of T cells expressing the γδ TCR. Analysis at a clonal level and TCR complementarity-determining region–3 spectratyping for γδ T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a γ4-δ3 TCR. Several γδ T cell clones displayed reactivity against CMV-infected cells. These observations are compatible with 2 non–mutually exclusive explanations for the γδ T cell predominance: a developmental advantage and infection-triggered, antigen-driven peripheral expansion. The patient carried the homozygous hypomorphic R561H RAG1 mutation leading to reduced V(D)J recombination but lacked all clinical features characteristic of Omenn syndrome. This report describes a new phenotype of RAG deficiency and shows that the ability to form specific antibodies does not exclude the diagnosis of SCID

γδ T-cell Receptors Derived from Breast Cancer–Infiltrating T Lymphocytes Mediate Antitumor Reactivity

γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCRs) from tumor-infiltrating γδ T lymphocytes (γδ TILs) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17. We characterized TCRγ or TCRδ chains of γδ TILs and observed a higher proportion of Vδ2+ T cells compared to other tumor types. By reconstructing matched Vδ2- TCRγ and TCRδ pairs derived from single-cell sequencing, our data suggest that γδ TILs could be active against breast cancer and other tumor types. The reactivity pattern against tumor cells depended on both the TCRγ and TCRδ chains and was independent of additional co-stimulation through other innate immune receptors. We conclude that γδ TILs can mediate tumor reactivity through their individual γδ TCR pairs and that engineered T cells expressing TCRγ and δ chains derived from γδ TILs display potent antitumor reactivity against different cancer cell types and, thus, may be a valuable tool for engineering immune cells for adoptive cell therapies.Fil: Janssen, Anke. University of Utrecht; Países BajosFil: Villacorta Hidalgo, Jose. Albert Ludwigs University of Freiburg; AlemaniaFil: Beringer, Dennis X. University of Utrecht; Países BajosFil: Van Dooremalen, Sanne. University of Utrecht; Países BajosFil: Febilla, Fernando. Utrecht University, Netherlands; ArgentinaFil: Van Diest, Eline. Utrecht University, Netherlands; ArgentinaFil: Terrizzi, Antonela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Bronser, Peter. Albert Ludwigs University of Freiburg; AlemaniaFil: Kock, Sylvia. Albert Ludwigs University of Freiburg; AlemaniaFil: Schmitt-Gräff, Annette. Albert Ludwigs University of Freiburg; AlemaniaFil: Werner, Martin. Albert Ludwigs University of Freiburg; AlemaniaFil: Fisch, Paul. Albert Ludwigs University of Freiburg; AlemaniaFil: Heise, Kerstin. University of Duisburg-Essen; AlemaniaFil: Follo, Marie. Albert Ludwigs University of Freiburg; AlemaniaFil: Straetemans, Trudy. University of Utrecht; Países BajosFil: Sebestyen, Zsolt. University of Utrecht; Países BajosFil: Chudakov, Dmitry M. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry; RusiaFil: Kasatskaya, Sofya A.. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry; RusiaFil: Kuball, Jurgen. University of Utrecht; Países BajosFil: Frenkel, Felix E.. No especifíca;Fil: Ravens, Sarina. Hannover Medical School; AlemaniaFil: Spierings, Eric. University of Utrecht; Países BajosFil: Prinz, Immo. Hannover Medical School; AlemaniaFil: Malkovsky, Miroslav. UW School of Medicine and Public Health; Estados UnidosFil: Fisch, Paul. Albert Ludwigs University of Freiburg; AlemaniaFil: Küppers, Ralf. University of Duisburg-Essen; Alemani