ABSTRACT
Regulatory T (Treg) cells induce immunologic tolerance by suppressing effector functions of conventional lymphocytes in the periphery. On the other hand, immune silencing is mediated by recognition of phosphatidylserine (PS) on apoptotic cells by phagocytes. Here we describe expression of the PS-binding protein Annexin V (ANXA5) in CD4+ CD25hi Treg cells at the mRNA and protein levels. CD4+ ANXA5+ T cells constitute about 0·1%-0·6% of peripheral blood CD3+ T cells, exhibit co-expression of several Treg markers, such as Forkhead box P3, programmed cell death protein-1, cytotoxic T-lymphocyte antigen-4 and CD38. In vitro, ANXA5+ Treg cells showed enhanced adhesion to PS+ endothelial cells. Stimulated by anti-CD3 and PS+ syngeneic antigen-presenting cells CD4+ ANXA5+ T cells expanded in the absence of exogenous interleukin-2. CD4+ ANXA5+ T cells suppressed CD4+ ANXA5- T-cell proliferation and mammalian target of rapamycin phosphorylation, partially dependent on cell contact. CD4+ ANXA5+ T-cell-mediated suppression was allo-specific and accompanied by an increased production of anti-inflammatory mediators. In vivo, using a model of delayed type hypersensitivity, murine CD4+ ANXA5+ T cells inhibited T helper type 1 responses. In conclusion, we report for the first time expression of ANXA5 on a subset of Treg cells that might bridge classical regulatory Treg function with immune silencing.
Subject(s)
Annexin A5/metabolism , Hypersensitivity, Delayed/immunology , Lymphocyte Activation , T-Lymphocytes, Regulatory/metabolism , Animals , Annexin A5/genetics , Annexin A5/immunology , Cell Adhesion , Cell Proliferation , Cells, Cultured , Cytokines/immunology , Cytokines/metabolism , Disease Models, Animal , Endothelial Cells/immunology , Endothelial Cells/metabolism , Humans , Hypersensitivity, Delayed/genetics , Hypersensitivity, Delayed/metabolism , Male , Mice, Inbred C57BL , Phenotype , Phosphatidylserines/metabolism , Phosphorylation , Signal Transduction , T-Lymphocytes, Regulatory/immunology , TOR Serine-Threonine Kinases/metabolism , Th1 Cells/immunology , Th1 Cells/metabolismABSTRACT
BACKGROUND: To study the value and safety of aqueous humor polymerase chain reaction (PCR) analysis for Herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus and Toxoplasma gondii in patients with uveitis. METHODS: Records of 45 consecutive patients with anterior and posterior uveitis who underwent AC paracentesis with PCR were reviewed. The main outcome measure was frequency of PCR positivity. Secondary outcomes were alteration of treatment, safety of paracentesis, and correlation of keratitic precipitates with PCR positivity, RESULTS: The overall PCR positivity was 48.9 % (22/45). Therapy was changed because of the PCR results in 14/45 patients (37.7 %). One patient experienced a paracentesis related complication (1/45, 2.2 %) without long-term sequelae. CONCLUSION: Aqueous PCR altered the diagnosis and treatment in over a third of our patients and was relatively safe. Aqueous PCR should be considered for uveitis of atypical clinical appearance, recurrent severe uveitis of uncertain etiology, and therapy refractory cases.
