Eosinophilic/T-cell chorionic vasculitis and chronic villitis involve regulatory T cells and often occur together.

Eosinophilic/T-cell chorionic vasculitis (ETCV) is characterized by mixed T-cell, eosinophilic, and histiocytic infiltrates within the chorionic vessel wall. We sought to better characterize this lesion with respect to other pathologic correlates and the T-cell populations involved. Epidemiologic data and other pathologic diagnoses, including concurrent chronic villitis (CV), were tabulated for each case of ETCV diagnosed at our institution over a 6-year period.

Immunohistochemical analysis reveals an influx of regulatory T cells and focal trophoblastic STAT-1 phosphorylation in chronic villitis of unknown etiology.

Maternal T cells and fetal macrophages constitute the primary infiltrate of chronic villitis of unknown etiology (CVUE), but the role of CD25(+)/FOXP3(+) regulatory T (Treg) cells in CVUE has not been examined. Moreover, little is known about the expression of immune markers, such as the major histocompatibility complex (MHC) class II antigen, human leukocyte antigen-DR (HLA-DR), in trophoblasts in this disease. We, therefore, examined CVUE placentas for the presence of Treg cells and aberrant activation of HLA-DR in trophoblasts.

Stem cell marker upregulation in normal cutaneous vessels following pulsed-dye laser exposure and its abrogation by concurrent rapamycin administration: implications for treatment of port-wine stain birthmarks.

Port-wine stains (PWS) represent a group of vascular malformations that are usually accompanied by psychological distress for affected patients, often reflected in high treatment demand. Although the pulsed-dye laser (PDL) was established as standard therapy for PWS more than a decade ago, therapeutic outcome may be unsatisfactory. One of the main drawbacks to successful PDL therapy is PWS revascularization shortly after laser exposure.

Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma.

Tumors contain variable numbers of lymphocytes, referred to as tumor infiltrating lymphocytes (TILs). In melanoma, the intensity of this lymphocytic infiltrate is believed to correlate with outcome, though there is some debate about the applicability of this finding for all melanomas. Much research has gone into classifying TILs with respect to antigen receptor structure and the antigen to which melanoma-specific T cells react.

KHSV(-) EBV(-) post-transplant effusion lymphoma with plasmablastic features: variant of primary effusion lymphoma?

Primary effusion lymphoma (PEL) is a rare type of B-cell non-Hodgkin lymphoma (NHL), which predominantly occurs in HIV-infected individuals, and is pathogenetically linked with Kaposi sarcoma (KS)-associated herpes virus/human herpes virus-8 (KSHV/HHV-8) infection with or without evidence of Epstein-Barr virus (EBV) co-infection. Although uncommon, PELs have been reported in immunocompetent patients and recipients of solid organ allografts. Rare cases of KSHV(-) EBV(+) post-transplant effusion lymphomas resembling PEL have also been described, as have KSHV(-) EBV(-) effusion lymphomas, the latter including those arising in individuals with chronic liver disease.

CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS.

Background: A 63-year-old female presented to her primary physician with numbness and weakness in her left leg, which progressed over several days to involve her entire lower extremities. MRI of the spine and brain revealed multiple metastases. The patient received ipilimumab and after 3 months experienced intermittent confusion and focal seizures.

Alpha-CTLA-4 mAb-associated panenteritis: a histologic and immunohistochemical analysis.

Monoclonal antibodies (mAbs) against the cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule are used as an adjuvant to experimental tumor immunization protocols in the treatment of malignant melanomas and ovarian cancers. Aside from noted early therapeutic successes, a spectrum of adverse effects, including severe gastroenteritis, has been reported. We report herein our observations of 5 patients who developed severe gastrointestinal toxicity affecting the gastric, small intestinal, and colonic mucosa.

Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory pathologies, raising the possibility that the therapeutic and toxic effects of CTLA-4 blockade might be linked.

Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of beta cells.

The pathogenesis of type 1 diabetes (T1D) involves the immune-mediated destruction of insulin-producing beta cells in the pancreatic islets of Langerhans. Genetic analysis of families with a high incidence of T1D and nonobese diabetic (NOD) mice, a prototypical model of the disorder, uncovered multiple susceptibility loci, although most of the underlying immune defects remain to be delineated. Here we report that aged mice doubly deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) manifest insulitis, destruction of insulin-producing beta cells, and compromised glucose homeostasis.

A novel T cell receptor transgenic animal model of seborrheic dermatitis-like skin disease.

We have characterized a novel animal model of the common inflammatory skin disease seborrheic dermatitis (SD) that involves the expression of the self-specific 2C transgenic T cell receptor on the DBA/2 genetic background. Opportunistic fungal pathogens are present in the primary histological lesions and severe disease can be mitigated by the administration of fluconazole, demonstrating a role for infection in disease pathogenesis. Spontaneous disease convalescence occurs at 70-90 d of age and is preceded by an expansion of CD4+ T cells that partially restores the T cell lymphopenia that occurs in these animals.

A comparison of thyroxine- and polyamine-mediated enhancement of rat facial nerve regeneration.

Thyroid hormones and spermidine, a motor neuron trophic polyamine (PA), have been shown to enhance peripheral motor nerve regeneration; however, the mechanism by which these treatment modalities exert their effect is unknown. Similarities in treatment outcome suggest that these molecules may be working via a common mechanism. Such an explanation is plausible since thyroid hormone is a potent inducer of ornithine decarboxylase (ODC), which is the rate-limiting enzyme involved in polyamine synthesis.