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This article discusses a case of infectious mononucleosis with secondary hemophagocytic lymphohistiocytosis (HLH) in a 4-year-old Japanese girl. The patient presented with symptoms such as prolonged high fever, bicytopenia, cervical lymphadenopathy, and hepatosplenomegaly. The bone marrow aspiration revealed the presence of epithelioid granulomas and a higher proliferative activity of T-lymphocytes. The authors suggest that the granulomas may be related to the antigen-presentation process and further studies are needed to analyze this. [Extracted from the article]

Purpose: A proposed etiopathogenesis of biliary atresia (BA) involves T-cell-mediated inflammatory bile duct damage and progressive hepatic fibrosis. Pediatric surgeons often observe swelling of the hepatic hilar lymph nodes during the Kasai procedure. Given the importance of regulatory mechanisms in immune responses, the present study was designed to analyze the quantitative changes of regulatory T cells ( T cells) in the hepatic hilar lymph nodes (hepatic hilar LNs) and peripheral blood (PB) in BA. Methods: The hepatic hilar LNs and PB obtained during the Kasai procedure were analyzed by flow cytometry. The ratios of total and active Tregs to the total CD4 cells in the PB and the hepatic hilar LNs were compared. Results: In patients with BA, the ratios of both the total and active T cells in the hepatic hilar LNs were higher than those in the PB (total T cells: PB vs. LN; P < 0.001; active T cells: PB vs. LN; P = 0.001). In BA patients, the increase in the ratio of active T cells to the CD4 + cells in the LNs in comparison to the PB was greater than that in control patients. The ratio observed in the BA patients was almost double the ratio observed in the control patients. The median LN/PB ratio in the BA patients was 3.1, while that in controls was 1.6 ( P = 0.03). Conclusion: The present study showed that the ratios of both total T cells and active T cells were higher in the hepatic hilar lymph nodes of BA patients. This finding could shed light on the pathogenesis of BA. [ABSTRACT FROM AUTHOR]

Background Although Helicobacter pylori eradication is a first-line treatment of gastric MALT lymphoma, roughly 25% of patients do not respond to treatment. CD4+ FOXP3+ regulatory T ( Treg) cells regulate immune responses in physiological conditions and various inflammatory conditions, including H. pylori-associated diseases. Our goal was to determine how Treg cells affect responsiveness to H. pylori eradication therapy. Materials and methods We performed dual immunohistochemistry for CD4 and FOXP3 to evaluate the prevalence of FOXP3+ Treg cells in the stomach of 63 patients with MALT lymphoma and 55 patients with chronic active gastritis. Receiver operating characteristic analysis was carried out to determine the best cut-off point in differentiating H. pylori eradication responders from nonresponders. Results Both the FOXP3+/ CD4+ cell ratio and the absolute number of FOXP3+ cells per high-power field in MALT lymphoma were significantly greater in H. pylori eradication responders compared with nonresponders, suggesting that Treg cells function in regression mechanisms of MALT lymphomas. Cut-off points with good sensitivities and specificities were obtained to predict eradication outcome. Conclusions A high number of Treg cells or a high ratio of Treg cells to the total number of CD4+ T cells in gastric MALT lymphoma could predict responsiveness to eradication therapy. [ABSTRACT FROM AUTHOR]

Granulomas are classified as immune or foreign body granulomas. Of these, the immune granulomas, a hallmark of granulomatous inflammation, are closely related to cell-mediated immune responses. The aim of the present study is to characterize immune granuloma cells in 33 patients with granulomatous inflammation focusing on the expression of CD205 ( DEC205), a cell surface marker of antigen presenting cells, and their spatial relationship to T cells. CD205 was frequently expressed by immune granuloma cells, in contrast to foreign body granuloma cells that lacked CD205 expression. T cells were not only distributed in a lymphocyte collar around the granuloma, but also present among the granuloma cells (termed 'intra-granuloma T cells'). Intra-granuloma T cells stained positive for Ki-67 (median positivity = 9.4%) by double immunostaining for CD3 and Ki-67. This indicated the presence of proliferative stimuli within the granuloma that could activate the intra-granuloma T cells. The labeling index of Ki-67 in intra-granuloma T cells was significantly higher than that of T cells in the lymphocyte collar ( P < 0.0001) or T cells in the T cell zone (paracortex) of chronic tonsillitis or reactive lymphadenitis ( P = 0.002). These data indicate a close similarity between immune granulomas and antigen presenting cells. [ABSTRACT FROM AUTHOR]

Hepatocellular necrosis may be complicated in the clinical course of T-cell lymphoma. Herein are reported two cases of peripheral T-cell lymphoma associated with a rapid increase of serum transaminases in their final course. The final diagnoses were enteropathy-type T-cell lymphoma of the jejunum (patient 1) and hepatosplenic T-cell lymphoma (patient 2). The livers of both patients had non-zonal, well-demarcated coagulation necrosis (approximately 70% in patient 1 and 40% in patient 2) that was infiltrated by lymphoma cells bearing a cytolytic granule content (granzyme B). Hepatocytes in the necrotic areas in patient 2 showed immunoreactivity for human simplex virus type 1. Although the mechanism of the hepatocyte necrosis is unclear, it is suggested that the hepatocyte submassive necrosis may be related to an infection complicated in the final course of lymphoma or by certain direct effects of the tumor cells. [ABSTRACT FROM AUTHOR]

In a recent report, [Zhang et al. (2003) N. Engl. i. Med. 348,203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; p = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a+ dendritic cells (DCs), factor XIIIa+ dermal DCs, and CD68+ macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a+ cells and factor XIIIa+ cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa+ cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a+ cells. Interestingly, factor XIIIa+ cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a+ cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. [ABSTRACT FROM AUTHOR]

Recently, it has been demonstrated that the skin-infiltrating T cells express cutaneous lymphocyte-associated antigen, which is the ligand of E-selectin or endothelial-leukocyte adhesion molecule, suggesting that cutaneous lymphocyte- associated antigen functions as the homing receptor of the skin infiltrating T cells. In contrast, the mechanism for the migration of Langerhans cells from the bone marrow to the skin has not been clarified. Sialyl LewisX acts as a ligand for endothelial-leukocyte adhesion molecule and granule membrane protein 140. We examined the expression of sialyl LewisX in epidermal dendritic cells in human skin. Two color immunofluorescence study on an epidermal sheet revealed that human leukocyte antigen DR+ or CD1a+ epidermal dendritic cells were partially sialyl LewisX+, although all of the sialyl LewisX+ dendritic cells were human leukocyte antigen DR+ and CD1a+. Further analysis of these dendritic cells by flow cytometry demonstrated that most of the human leukocyte antigen DR+ and CD1a+ epidermal cells expressed sialyl LewisX, although the magnitude of its expression was more variable than that of CD1a expression, and that some of human leukocyte antigen DR+ cells were clearly sialyl LewisX-. Immunoperoxidase study of normal skin showed the presence of sialyl LewisX+ dendritic cells not only in the epidermis but also in the upper dermis. These data demonstrating the heterogeneity of the expression of sialyl LewisX by epidermal Langerhans cells suggest their possible relationship to the stage of maturation as well as to the migration of Langerhans cells from the bone marrow to the skin. [ABSTRACT FROM AUTHOR]