Proinflammatory T helper type 17 cells are effective B-cell helpers

T helper type 17 (TH17) cells are highly proinflammatory effector T cells that are characterized by the production of high amounts of IL-17A, IL-17F, IL-21, and IL-22. Furthermore, TH17 cells have been associated with a number of autoimmune diseases. However, it is not clear whether TH17 cells can also serve as effective helper cells. Here we show that TH17 cells can function as B-cell helpers in that they not only induce a strong proliferative response of B cells in vitro but also trigger antibody production with class switch recombination in vivo. Transfer of TH17 cells into WT or T-cell receptor α–deficient mice, which lack endogenous T cells, induces a pronounced antibody response with preferential isotype class switching to IgG1, IgG2a, IgG2b, and IgG3, as well as the formation of germinal centers. Conversely, blockade of IL-17 signaling results in a significant reduction in both number and size of germinal centers. Whereas IL-21 is known to help B cells, IL-17 on its own drives B cells to undergo preferential isotype class switching to IgG2a and IgG3 subtypes. These observations provide insights into the unappreciated role of TH17 cells and their signature cytokines in mediating B-cell differentiation and class switch recombination.     

Th9与支气管哮喘

支气管哮喘(简称哮喘)是一种由多种细胞如淋巴细胞、嗜酸粒细胞、肥大细胞等及其细胞组分参与的气道慢性炎症疾患,Th2细胞被认为是哮喘发病机制中的主要效应细胞.长期以来,白介素9(IL-9)都被认为是Th2类细胞因子,在变应性疾病,尤其是过敏性哮喘、变应性鼻炎等发病机制中起着重要的作用.近年来研究发现,机体内可能存在着一群...     

Th9与支气管哮喘

支气管哮喘（简称哮喘）是一种由多种细胞如淋巴细胞、嗜酸粒细胞、肥大细胞等及其细胞组分参与的气道慢性炎症疾患,Th2细胞被认为是哮喘发病机制中的主要效应细胞。长期以来,白介素9（IL-9）都被认为是Th2类细胞因子,在变应性疾病,尤其是过敏性哮喘、变应性鼻炎等发病机制中起着重要的作用。近年来研究发现,机体内可能存在着一群新型的不同于目前已知Th1、Th2及Th17等效应细胞,被称之为＂Th9＂细胞。Th9细胞在转化生长因子-β及IL-4联合刺激下分化而来,具有分泌IL-9和IL-10的能力。Th9细胞作为效应性T细胞,在促进组织炎症发生的过程中起着重要作用。现就Th9细胞的生物学功能及与哮喘的关系进行简要综述。     

Modulation of the immunological response to hepatitis B virus by antibodies

Antibodies to HBsAg of IgG class enhanced the helper activity of a human T cell clone to promote the in vitro synthesis of immunoglobulins by autologous B lymphocytes. Using two different assay systems, the effect of antigen-specific antibodies on the helper function of a HBsAg-reactive T cell clone was studied. The monoclonal antibody to HBsAg A5C3 (IgG) increased significantly the T cell-dependent production of immunoglobulins by Staphyloccocus aureus-stimulated autologous B lymphocytes. Furthermore, the results obtained with a different type of assay showed that A5C3 also increased the synthesis of antibody to HBsAg by the autologous B cells in the presence of HBsAg and the helper T cell clone. On the other hand, when the monoclonal antibody to HBsAg of IgM class, H5D3 or the F(ab')2 fragment of A5C3 were tested, no significant enhancement of the helper activity of the T cell clone was observed. Experiments performed in mice showed that the in vivo antibody to HBsAg response to low concentrations of HBsAg was significantly enhanced by mixing this antigen with monoclonal antibody to HBsAg of IgG class. No effect was observed when a monoclonal antibody to HBsAg of IgM class was used to prepare the immune-complexed immunogen. The results presented here suggest that antibodies play a critical role in their own production through regulating the activity of helper T cells. This phenomenon might contribute to the increased antibody synthesis of in vivo secondary immune responses and could be of use in designing more efficient vaccine programs in man.     

Lymphocytes T et allergie alimentaire

The pathogenesis of food allergy was, in the past, focused on atopy, IgE and auxiliary lymphocytes responsible for class switching. Nevertheless, some allergic reactions induced by foods do not involve IgE. Mechanisms of breaking tolerance and cell mechanisms at the level of the gut mucosa are now better understood. This analysis of the involvement of lymphocytes in food allergy will begin with comments on presentation of antigens in Peyer's patches, followed by comments on a recognition mechanism involving surface receptors and regulation by chemokines. In association with intestinal immunity, regulatory T cells have a central role in the induction of immunization or tolerance to foods.     

Synovial fluid lymphocytes in rheumatoid arthritis

There is significant evidence implicating immunologic mechanisms in the pathogenesis of rheumatoid arthritis (RA). To investigate the possibility that a cellular imbalance of T and B lymphocytes plays a role in perpetuating synovitis, an examination of the peripheral blood and synovial fluid lymphocytes of patients with seropositive rheumatoid arthritis was undertaken. A significant lymphopenia was encountered in RA patients, with values approximately midway between those in normal controls and the severe lymphopenia seen in a group of patients with systemic lupus erythematosus. A significantly greater diminution of T than B cells was noted in RA, and normal percentage distributions of lymphocytes in peripheral blood were documented. Normal percentages of T and B cells, similar to those in peripheral blood, were found in synovial fluids of patients with seropositive RA, seronegative RA, osteoarthritis, and gout. Two seropositive patients exhibited synovial fluid, but not peripheral blood, lymphocytes that stained both for IgG and IgM. These cells regenerated predominantly IgM after trypsinization and short-term culture with significant diminution of cells staining for IgG. It is postulated that double staining was secondary to surface immunoglobulins with rheumatoid factor activity binding intraarticular IgG. Such cells were not detected in peripheral blood in any of the groups of patients studied.     

Impaired IgA class switching in APRIL-deficient mice

The tumor necrosis factor (TNF) family member APRIL binds to the receptors BCMA on B cells and TACI on B and T cells. To investigate the role of APRIL in immunity, we generated APRIL-deficient mice. APRIL(-/-) mice have normal T and B lymphocyte development, normal T and B cell proliferation in vitro, but increased numbers of CD44(hi)CD62L(lo) CD4(+) effector/memory T cells and increased IgG responses to T-dependent antigens. Serum IgA levels were significantly decreased, and serum IgA antibody responses to mucosal immunization with TD antigens and to type 1 T-independent antigens were impaired in APRIL(-/-) mice. APRIL by itself induced IgA as well as IgG1 isotype switching in CD40-deficient IgM(+)IgD(+) sorted B cells. These results suggest that APRIL down-regulates T cell-dependent antibody responses and promotes IgA class switching.     

滤泡辅助T细胞相关分子与支气管哮喘

滤泡辅助性T细胞(T follicular helper cells,Tfh)是近来发现的CD4+T细胞亚群,它能够迁移至次级淋巴中心的B细胞滤泡,促进生发中心反应,包括调节生发中心的形成、发展和成熟以及辅助B细胞产生具有免疫功能的球蛋白及影响类别转换.Tfh能连续产生趋化因子受体5,在其配体CXCL13的作用下,外周的Tfh被募集至生发中心的B淋巴滤泡,参加生发中心的形成.诱导性共刺激分子和CO40L可以与B细胞表面的配体结合可以调节Tfh分泌IL-21参与B细胞的免疫应答,参与体液免疫.支气管哮喘(简称哮喘)发病机制复杂,T淋巴细胞在哮喘的气道炎症反应中起重要作用.本文回顾了Tfh细胞相关分子在哮喘气道炎症中的作用.     

DNA-daunorubicin complexes specifically suppress in vitro spontaneous anti-DNA antibody production in lymphocytes of patients with systemic lupus erythematosus

Elevated production of anti-DNA antibody in patients with systemic lupus erythematosus (SLE) is a central problem in the pathogenesis of tissue injury. In the present study, we attempted to manipulate anti-DNA antibody production through the antigen-cytotoxic drug conjugates, DNA-daunorubicin complexes. The effect of DNA-daunorubicin complexes was determined by examining SLE lymphocytes for spontaneous in vitro production of anti-DNA antibody. These complexes, at 2 μg/ml, suppressed anti-DNA antibody production, but not total IgG production, which suggests that specific suppression of anti-DNA antibody production was achieved at this concentration. We believe that the DNA-daunorubicin complexes affected mainly B cells, since such suppression was obtained by treating B cells, as well as B plus T cells. Furthermore, the complexes had no effect on the proliferative responses of SLE T cells to DNA, phytohemagglutinin, or concanavalin A. These results indicate that DNA-daunorubicin complexes may have the potential for selectively suppressing anti-DNA antibody production in patients with SLE.     

NK T cells provide lipid antigen-specific cognate help for B cells

The mechanisms of T cell help for production of antilipid antibodies are largely unknown. This study shows that invariant NK T cells (iNK T cells) and B cells cooperate in a model of antilipid antigen-specific antibody responses. We use a model haptenated lipid molecule, 4-hydroxy-3-nitrophenyl-alphaGalactosylCeramide (NP-alphaGalCer), to demonstrate that iNK T cells provide cognate help to lipid-antigen-presenting B cells. B cells proliferate and IgG anti-NP is produced from in vivo-immunized mice and in vitro cocultures of B and NK T cells after exposure to NP-alphaGalCer, but not closely related control glycolipids. This B cell response is absent in CD1d(-/-) and Jalpha18(-/-) mice but not CD4(-/-) mice. The antibody response to NP-alphaGalCer is dominated by the IgM, IgG3, and IgG2c isotypes, and marginal zone B cells stimulate better in vitro lipid antigen-driven proliferation than follicular B cells, suggesting an important role for this B cell subset. iNK T cell help for B cells is shown to involve cognate help from CD1d-instructed lipid-specific iNK T cells, with help provided via CD40L, B7-1/B7-2, and IFN-gamma, but not IL-4. This model provides evidence of iNK T cell help for antilipid antibody production, an important aspect of infections, autoimmune diseases, and vaccine development. Our findings also now allow prediction of those microbial antigens that would be expected to elicit cognate iNKT cell help for antibody production, namely those that can stimulate iNKT cells and at the same time have a polar moiety that can be recognized by antibodies.     

Spontaneous immunoglobulin secreting cells in idiopathic usual interstitial pneumonia

Abundant evidence suggests that activation of B lymphocytes and formation of immune complexes play important roles in the pathogenesis of idiopathic pulmonary fibrosis. We investigated the level of B lymphocyte activation in patients with idiopathic UIP (n = 10, all were biopsy proven cases), for the purpose of evaluating its role. In order to determine the level of B lymphocyte activation, the number of spontaneous immunoglobulin secreting cells in blood was counted by using reverse hemolytic plaque assay. The number of IgA and IgG secreting cells significantly increased in patients with idiopathic UIP when compared with those in healthy controls (n = 8). The number of IgG secreting cells also significantly increased in patients with IP-CVD, but no significant increase in the number of Ig secreting cells could be detected in patients with pulmonary emphysema, diffuse panbronchiolitis or sarcoidosis. The study of cell surface markers revealed significant increase of CD21 (B2 and OKB7) positive cells in patients with idiopathic UIP. CD21 positive cells were immature B lymphocytes. These results suggest that increase of resting B lymphocytes and immunoglobulin secreting cells occurred and that the differentiation of B lymphocytes may be accelerated in idiopathic UIP. Furthermore, there is the possibility that soluble factors produced by T lymphocytes influenced the function of B lymphocytes in our experiment.     

Increased spontaneous and lymphokine-conditioned IgA and IgG synthesis by B cells from alcoholic cirrhotic patients.

Immunoglobulin secretion by B lymphocytes is a complex process in which lymphokines secreted by T lymphocytes play an important regulatory role. Increased serum levels of IgA and IgG have been characteristically detected in patients with alcoholic cirrhosis. We have studied the functional alterations of T and B lymphocytes implicated in the physiopathology of this common immunoglobulin abnormality. After activation with phytohemagglutinin, purified T cells from alcoholic cirrhotic patients showed significantly enhanced secretion of B-cell differentiation factors for IgG and IgA with respect to those secreted by T cells from healthy controls (p less than 0.05). Simultaneously, normal secretion of B-cell differentiation factor for IgM was demonstrated in T lymphocytes from these patients. The pattern of secretion of the lymphokines involved in the regulation of the B-cell differentiation pathway found in alcoholic cirrhotic patients was different from that of the primary biliary cirrhotic patients studied. Purified B cells from patients with alcoholic cirrhosis secreted significantly higher amounts of IgA and IgG than did those found in healthy controls, both spontaneously (p less than 0.05) and after sequential activation with immunoglobulin ligands (Staphylococcus aureus Cowan I) and a standard B-cell differentiation factor preparation (p less than 0.05). By contrast, the IgM secretion and regulatory pathway were normal in alcoholic cirrhotic patients. These results support a physiopathological explanation for the characteristic hyperimmunoglobulinemia found in patients with alcoholic cirrhosis.