Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo.

A murine model of peritonitis was used to test the role of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in acute inflammation. A monoclonal antibody (mAb) specific for murine PECAM-1 injected intravenously 4 h before the intraperitoneal injection of thioglycollate broth blocked leukocyte emigration into the peritoneal cavity for up to 48 h. This block was particularly evident for neutrophils. Control mAb, including one that bound to murine CD18 without blocking its function, failed to block emigration when used at the same or higher concentrations. The decreased emigration seen with the anti-PECAM-1 antibody was not due to neutropenia or neutrophil sequestration in the lung, spleen, or other organs; peripheral blood leukocyte counts were not diminished in these mice. In the mesenteric venules of the mice treated with anti-PECAM-1 mAb, leukocytes were frequently seen in association with the luminal surface of the vessel, but did not appear to emigrate. Thus, the requirement for PECAM-1 in the transendothelial migration of leukocytes previously seen in an in vitro model holds true in this in vivo model of acute inflammation.

Immunophenotypic identification of Sezary cells in peripheral blood.

Despite anecdotal literature that Sezary cells express the CD4+ CD7- immunophenotype, no formal validation has been published establishing the use of this immunophenotype for clinical or experimental purposes. Consequently, the only method presently available for Sezary cell identification is nuclear contour analysis, a labor-intensive procedure not generally available at most major medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for the identification of Sezary cells was examined. The study found that the percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration correlates with enumeration by nuclear contour analysis in most patients (11 of 15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly, CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes, as measured using V beta-specific T-cell receptor monoclonal antibodies. The study found this method to be exceptionally accurate, with two caveats: (1) the absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio is uninformative; and (2) in approximately 25% of patients with an elevated CD4/CD8 ratio, the Sezary cells are CD7+.

Sezary lineage cells can be induced to proliferate via CD28-mediated costimulation.

Sezary syndrome and mycosis fungoides are related chronic lymphoproliferative diseases caused by the malignant growth of CD4+ T lymphocytes that display hyperconvoluted nuclei and a predilection for skin homing. Despite the malignant nature of these cells, they paradoxically do not grow in vitro, either spontaneously or following exposure to mitogens. Partly because of this technical limitation, the cellular lineage and causes of abnormal growth resulting in a classical hyperconvoluted Sezary cell are poorly characterized. To better understand these aspects, we examined Sezary lineage cell growth in vitro. We found that, contrary to previous reports, Sezary lineage cells are capable of in vitro proliferation in response to either PHA or anti-CD3 mAb, if exogenous costimulation is provided. The CD28-B7 interaction provides at least one of the costimulatory signals capable of inducing Sezary lineage cell growth. Namely, Sezary lineage cells from three of six Sezary syndrome patients proliferated in response to PHA if an anti-CD28 mAb was also added to the in vitro culture. The remaining three patients' Sezary lineage cells were dependent upon CD28-B7-mediated costimulation, but in addition required other intercellular signals present on blood mononuclear cells. The relative lack of costimulation from the patients' own PBMC is not due to an intrinsic defect in the mycosis fungoides/Sezary syndrome patients' immune accessory cells. Rather, it appears primarily due to an inability of Sezary cells to significantly up-regulate CD40 ligand (gp39) following in vitro exposure to PHA.

[Granulomatous cheilitis. Case report]. / Kokkiomatodes cheilitida. (Anaphora periptoseos)

A case of granulomatous cheilitis, an uncommon disease that is difficult to be treated is described. The disease is of unknown etiology and it may represents a monosymptomatic form of Melkersson-Rosenthal syndrome. The significance of the clinical lesions, the microscopic features as well as the recent aetiological aspects of the disease are discussed.

In situ analysis of cytokine responses in experimental murine schistosomiasis.

BACKGROUND: Infection with schistosomiasis results in CD4+ T helper (Th) cell-dependent granulomatous inflammation around parasite eggs. T cell-derived cytokines play a critical role in the induction and subsequent down-modulation of the granulomas. These cytokine responses have been previously examined in lymphoid cell supernatants or in tissue homogenates but have not been examined directly in the local microenvironment of the lesions or in the reacting lymphoid tissues. EXPERIMENTAL DESIGN: With the use of specific mAb, the cytokines IL-2, IFN gamma, IL-4, and IL-10 were investigated by direct immunocytochemical analysis in situ in hepatic egg granulomas and lymphoid organs from acutely and chronically infected mice. Cytokine expression in situ was compared with cytokine production during a secondary response in vitro. RESULTS: All cytokines examined were detected in various amounts in both the hepatic egg granulomas as well as in mesenteric lymph nodes and spleen. The majority of cells expressing the cytokines was found in lymph nodes, and very few were found in granulomas. Relatively small numbers of granulomas contained most of the cytokine-expressing cells, which tended to localize in their periphery. Granulomas and lymphoid organs in the acute disease contained significantly more cytokine-expressing cells in comparison with those from the chronic disease. This observation correlated well with cytokine production in vitro. CONCLUSIONS: Direct immunocytochemical examination in situ was used to detect and measure cytokine-producing cells in hepatic egg granulomas and reacting lymphoid organs of acute and chronic experimental murine schistosomiasis. Observed cytokine patterns suggest that granulomas contain T lymphocytes of both the Th-1 and Th-2 types and that cytokine production occurs during a limited time in the early granuloma. The immunocytochemical technique affords a direct appraisal of amount, dynamics, and localization of cytokine-producing cells in the unperturbed local environment.