IntroductionSeveral subsets of stromal cells, in particular follicular dendritic cells (FDCs) and fibroblastic reticular cells (FRCs), are found within secondary lymphoid organs where they play a key role in the initiation and maintenance of efficient immune responses. FDCs are restricted to germinal centers (GCs) and allow B-cell migration, selection, and differentiation through a complex set of survival factors including BCR-mediated signal, chemokines, cytokines, and adhesion molecules. 1 B-cell selection relies on an affinitybased competition for the fixation of antigen, presented as immune complexes by CD21 hi CD35 hi FDCs. Only B cells with high-affinity BCR receive survival signals from FDCs, capture antigen, and present it to CD4 ϩ T cells that deliver additional survival and maturation signals. 2,3 Conversely, FRCs are less well characterized. They are tightly interconnected in the paracortex of lymph nodes (LNs) where they secrete and ensheath various extracellular matrix components, thus building an intricate network of conduits, connecting afferent lymphatic vessels to high endothelial venules (HEVs). 4 This conduit system allows the rapid transport of soluble antigens from the periphery to the resident myeloid immature dendritic cells (DCs). 5 In addition, part of this reticular network called cortical ridge favors B, T, and DC recruitment and reciprocal interactions, in particular through the production of constitutive and inflammatory chemokines. 6,7 CCL19, CCL21, and CXCL12 are involved in the migration of mature myeloid DCs and naive B and T cells, whereas CXCL9, CXCL10, and CCL5 are crucial for the migration of activated T cells and plasmacytoid DCs. [8][9][10] Strikingly, CCL19 and CCL21 are not synthesized by human HEVs but rather by stromal cells in the T-cell zone. 11,12 These chemokines further reach luminal surface of HEVs by endothelial uptake and transcytosis. FRCs provide therefore a favorable and highly specialized lymphoid environment for immune cell migration and activation.The ontogeny of FRCs and FDCs remains unclear, but these cells are supposed to be of mesenchymal origin. LN organogenesis in the mouse relies on the interaction between CD45 Ϫ VCAM-1 ϩ ICAM-1 ϩ mesenchymal cells and CD45 ϩ CD4 ϩ CD3 Ϫ lymphoid tissue inducer cells in the LN anlagen. 13 A prominent role is attributed to lymphotoxin-␤ receptor (LT␤R) triggering by membrane-bound LT␣1␤2 (LT) and to tumor necrosis factor receptor 1 (TNFR1)/tumor necrosis factor-␣ (TNF). 14,15 Adult lymphoid tissues are highly dynamic structures that retain several features of embryonic organization. 16 Functional mouse FRCs able to construct a reticular meshwork and to secrete inflammatory chemokines could be generated in vitro by stimulation of LN-derived stromal cell lines using a combination of TNF and LT. 17 In vivo, transgenic expression of LT or injection of newborn LN-derived The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefo...

Accumulating evidences indicate that the cellular and molecular microenvironment of follicular lymphoma (FL) has a key role in both lymphomagenesis and patient outcome. Malignant FL B cells are found admixed to specific stromal and immune cell subsets, in particular CD4 pos T cells displaying phenotypic features of follicular helper T cells (T FH ). The goal of our study was to functionally characterize intratumoral CD4 pos T cells. We showed that CXCR5 hi ICOS hi CD4 pos T cells sorted from FL biopsies comprise at least two separate cell populations with distinct genetic and functional features: (i) CD25 pos follicular regulatory T cells (T FR ), and (ii) CD25 neg T FH displaying a FL-B cell supportive activity without regulatory functions. Furthermore, despite their strong similarities with tonsil-derived T FH , purified FL-derived T FH displayed a specific gene expression profile including an overexpression of several genes potentially involved directly or indirectly in lymphomagenesis, in particular TNF, LTA, IL4 or CD40LG. Interestingly, we further demonstrated that these two last signals efficiently rescued malignant B cells from spontaneous and rituximab-induced apoptosis. Altogether, our study demonstrates that tumor-infiltrating CD4 pos T cells are more heterogeneous than previously presumed, and underlines for the first time the crucial role of T FH in the complex set of cellular interactions within FL microenvironment.

Human mesenchymal stem cells (MSC) strongly repress activated T-cell proliferation through the production of a complex set of soluble factors, including the tryptophancatabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which is induced by IFN-;. Conversely, MSCs support survival of follicular lymphoma (FL) B cells, in particular after exposure to tumor necrosis factor-A (TNF) and lymphotoxin-A1B2 (LT). The role of MSCs on normal and malignant B-cell growth in steady-state and inflammatory conditions remains to be fully explored. We show here that resting MSCs sustain activated normal B-cell proliferation and survival, whereas IFN-;-conditioned MSCs mediate IDOdependent B-cell growth arrest and apoptosis. IFN-;, TNF, and LT are significantly overexpressed by the microenvironment of invaded FL-lymph nodes, but their relative expression patterns are highly heterogeneous between samples. In vitro, IFN-; abrogates the B-cell supportive phenotype induced by TNF and LT on MSCs. Moreover, IFN-; overrules the growth promoting effect of MSCs on primary purified FL B cells. Altogether, these results underline the crucial role of the cytokine context in the local crosstalk between malignant cells and their microenvironment and provide new insights into our knowledge of the FL cell niche that emerges as a new promising target for innovative therapeutic strategies. [Cancer Res 2009;69(7):3228-37]

The implementation of interdisciplinarity in the work routine of the family health care team

In follicular lymphoma (FL), follicular helper T cells (TFH) have been depicted as one of the main components of the malignant B-cell niche and a promising therapeutic target. Although defined by their capacity to sustain FL B-cell growth together with specific gene expression and cytokine secretion profiles, FL-TFH constitute a heterogeneous cell population. However, specific markers reflecting such functional heterogeneity are still lacking. In this study, we demonstrate that CD10 identifies a subset of fully functional germinal center TFH in normal secondary lymphoid organs. Importantly, this subset is amplified in the FL context, unlike in other B-cell lymphomas with a follicular growth pattern. Furthermore, whereas FL-TFH produce high levels of interleukin (IL)-21 and low levels of IL-17 irrespectively of their CD10 expression, CD10(pos) FL-TFH specifically exhibit an IL-4(hi)IFN-γ(lo)TNF-α(hi) cytokine profile associated with a high capacity to sustain directly and indirectly malignant B-cell survival. Altogether, our results highlight the important role of this novel functional subset in the FL cell niche.

Allergic rhinitis is a common disease in childhood, but nasal cytology is rarely used by pediatricians. We compared two techniques of cell sampling, brushing and blowing the nose, among 77 children suffering from chronic rhinitis, of whom 59 were allergic. Staining by the May‐Griinwald‐Giemsa method enabled the evaluation of the density of cells and especially differential counting of the inflammatory cells. Staining by the Luna method was used as a control for the eosinophils. For the eosinophil count, we found a strong correlation between the two methods of collecting the nasal secretions (r= 0.96). Because blowing the nose is painless and easy to perform, it is more appropriate than brushing in routine use for the diagnosis of allergic rhinitis in children and in nasal challenge with allergens.

A total of 106 children suffering from perennial rhinitis and/or asthma, and all allergic to Dermatophagoides pteronyssinus (DP), underwent nasal provocation challenge (NPC) with DP to determine the best method of diagnosis. Posterior rhinomanometry was uninterpretable in 17 patients and gave negative results in 31. Clinical scores for sneezing and rhinorrhea were more effective but did not diagnose the disorder in 11 children. However, nine of the 11 had significant increases in eosinophil count in the late phase. Clinical scores and cytology were also useful for assessing whether NPC with allergens was positive in children. The feasibility and safety of NPC with DP are high for rhinitic and stable asthmatic patients, but mild reactions may occur during the late phase.

Describes decapods (including new species) from Cretaceous and lower Tertiary deposits of western Senegal, French West Africa.