Toxoplasmic myositis as a presenting manifestation of idiopathic CD4 lymphocytopenia

Toxoplasma gondii encysts in skeletal muscle. Although only rarely found at muscle biopsy, this parasite has previously been regarded as a possible cause of polymyositis. We report a case of biopsy-proven toxoplasmic myositis in a non-HIV-infected patient that led to recognition of idiopathic CD4 lymphocytopenia (ICL), a rare condition typically associated with opportunistic infections. Interestingly, the CD25(+) subset that corresponds to the CD4(+) regulatory T cells controlling autoimmune processes was lacking. Steroid and antiprotozoal therapy led to recovery.     

A closed and single-use system for monocyte enrichment: potential for dendritic cell generation for clinical applications

BACKGROUND: This study evaluated the ability of a modified cell separator (Cobe Spectra Apheresis) system to isolate monocytes (MOs) by elutriation. The evaluation was performed in two independent international laboratories. The capacity of collected MOs to differentiate into dendritic cells (DCs) was also assessed. STUDY DESIGN AND METHODS: MNCs from platelet apheresis residues were elutriated on a modified cell separator (Cobe Spectra Apheresis system) using a custom disposable set. Cells were separated according to their size and density. Recovery and purity of the collected cell product were evaluated by impedance counting and flow cytometry. DCs were differentiated in culture from the elutriated MOs and characterized by their surface markers and stimulatory capacity in a mixed WBC reaction assay. RESULTS: Six apheresis mononuclear cell products were used by each laboratory. The separation was achieved in less than 1 hour. Collected MOs had the potential to differentiate into DCs. CONCLUSION: The modified cell separator is an easy and fast device to obtain highly enriched MOs with a DC differentiation potential. The system is closed and employs a single-use disposable set and is more amenable to good tissue practice. This method could become a valuable tool for DC-based active immunotherapy.     

CD3-T cell receptor modulation is selectively induced in CD8 but not CD4 lymphocytes cultured in agar.

The CD3-T cell receptor (TcR) complex is central to the immune response. Upon binding by specific ligands, internalized CD3-TcR molecules increase, and either T cell response or unresponsiveness may ensue depending on the triggering conditions. Using semi-solid agar culture, we have shown previously that quiescent CD4 but not CD8 lymphocytes generate clonal colonies under phytohaemagglutinin stimulation. Here we have demonstrated that the agar induces selective CD3-TcR modulation in the CD8 and not in the CD4 subset. CD8 lymphocytes preactivated in liquid culture and recultured in agar with exogenous recombinant interleukin-2 generate colonies with a modulated CD3-TcR surface expression. The peptides composing the CD3-TcR complex are synthesized in CD8 colonies as well as in CD4; however, the CD3 gamma chain is phosphorylated at a higher level in CD8 colonies. A component of the agar polymer, absent in agarose, appears to be the ligand that induces differential CD3-TcR modulation in the CD8 subset. In contrast to agar culture, CD8 colonies can be derived from quiescent CD8 lymphocytes in agarose. These CD8 colonies express unmodulated CD-TcR. CD3-TcR modulation with anti-CD3 monoclonal antibody prior to culturing in agarose inhibits the colony formation. We conclude that given triggering conditions can result in both CD3-TcR modulation and inhibition of the proliferative response selectively in the CD8 lymphocyte subset and not in the CD4.     

Separation of large quantities of mononuclear cells from human blood using a blood processor

A blood processor (IBM 2991) was used to separate lymphocytes from large volumes of blood. The procedure included the centrifugation of 200 ml whole blood on a density gradient. The results of this procedure were compared with those obtained with a manual procedure. Mononuclear cell (MNC) viability was preserved well in the two methods. But with the processor, recovery of MNC was better (63.5 +/- 2.5%) than with manual separation (26.5 +/- 4.1%). Monoclonal antibodies were used to identify the various cell subsets in the MNC fractions. No particular cell selection was observed when MNC fractions were obtained by the separator. In conclusion, the use of a cell separator provided an efficient technique for rapid isolation of large quantities of lymphocytes.     

The regulatory/cytotoxic graft-infiltrating T cells differentiate renal allograft borderline change from acute rejection

The interpretation of cellular infiltrate from renal transplant recipients with borderline (BL) changes is still a challenging problem. To analyze the immune phenotype of such infiltrate, we quantified the mRNA expression of Foxp3 and interleukinL-10 and granzyme B (GB) in 15 kidney biopsies with BL changes. Controls were patients presenting type IA acute rejection and nonrejecting patients. Only levels of GB mRNA correlated significantly with response to antirejection therapy. Levels of Foxp3 mRNA in BL changes were intermediate between type IA acute rejection and nonrejecting controls. To determine the balance of alloagressive to graft-protecting T cells, we quantified the Foxp3/GB ratio. BL changes T cells infiltrate expressed a significantly higher Foxp3/GB ratio than that in IA acute rejection. These results suggest that T cell infiltrate from BL change exhibit a tolerogenic rather than a cytotoxic phenotype.     

Clonal T-cell colony formation in agar culture: an attractive assay to test the T-cell depletion from bone marrow

Current studies suggest that the depletion of T-lymphocytes from donor marrow is an effective method for preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation in man. To deplete the T-lymphocytes from bone marrow cells we use either monoclonal anti-T-cell antibodies and complement or T101 ricin A-chain immunotoxin. Residual T-lymphocytes are analyzed by their capacity to form clonal T-cell colonies in the presence of phytohemagglutinin (PHA), accessory cells, and recombinant interleukin 2. The method is compared to immediate indirect immunofluorescence (iF) and thymidine incorporation by marrow cells stimulated by PHA. IF is not suitable for evaluating the depletion by immunotoxin, and the interpretation of thymidine incorporation is generally questionable. The results of the colony formation show that the sensitivity of the colony assay is close to that of iF when T cells are depleted by complement lysis, and the sensitivity of the colony assay is not dependent upon the depletion procedure. Therefore, the T-cell colony assay is a simple functional control for the quality of bone marrow T-cell depletion, especially for T-cell depletion by immunotoxin.     

Protein-losing enteropathy in gastrointestinal sarcoidosis associated with malignant lymphoma.

A patient with disseminated gastrointestinal sarcoidosis and non-Hodgkin's malignant lymphoma developed diarrhea and polyadenopathy. Laboratory analysis revealed the presence of protein-losing enteropathy without biological signs of malabsorption. Gastrointestinal biopsy specimens showed numerous sarcoidosis nodules without neoplastic proliferation in the stomach, small intestine, and rectum. The patient's course was favorable after treatment with prednisone and chlorambucil. Disseminated gastrointestinal sarcoidosis may be a previously unidentified cause of protein-losing enteropathy.     

Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases

A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur.
We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell-lymphomas diagnosed during a 5-year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease-free with an overall median follow-up of 30 months. Histologically, some distinctive signs such as epidermal pseudoepitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.     

Hepatic vein obstruction in idiopathic hypereosinophilic syndrome

We report an association between idiopathic hypereosinophilic syndrome and obstruction of the hepatic veins (Budd-Chiari syndrome). Budd-Chiari syndrome was assessed by liver biopsy and hepatic phlebography and documented by computed tomography. Postmortem examination revealed fibrous occlusion of the hepatic venous tree, as well as fibrosis of the endocardium and of myocardial and pulmonary vessels. To our knowledge, the association between idiopathic hypereosinophilic syndrome and Budd-Chiari syndrome has never previously been reported. Since it has been suggested that hypereosinophilia might cause endothelium damage, a link between these two entities is postulated.     

Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Evidence for a monoclonal T-cell lymphoproliferative disorder

Lymphomatoid granulomatosis (LG) and polymorphic reticulosis (PR), originally described as distinct entities, now are considered as a single disease process. Common histopathologic features include necrosis, vasculitis, and a granulomatous infiltrate. Such features have led to consider lymphomatoid granulomatosis as a systemic vasculitis; alternatively the possible emergence of an overt lymphoma has suggested that it could be a lymphoproliferative process. To investigate this later hypothesis, the authors analyzed the cellular infiltrate of tissue specimens from two patients with histologic features of LG. The analysis included the study of T-cell antigen expression and DNA rearrangement of the beta T-cell receptor gene. In one patient, the T-cell phenotype of infiltrating cells was abnormal because of antigen loss. In both patients, the cells contained rearranged DNA indicating the presence of a clonal T-cell proliferation. It is concluded that some cases of LG and PR, if not all, are related to a neoplastic T-cell lymphoproliferative disorder.