Regulation of T cell development by c-Cbl: essential role of Lck
A canonical pre-TCR/TCR signaling pathway critical for thymic T cell development involves sequential phosphorylation and signaling through Lck, Zap70, Lat and Slp76. However, we and others have previously reported that genomic deletion of c-Cbl (Cbl) partially or completely reverses the defects in thymic development in mice deficient in Zap70, Slp76, Lat or Vav1, indicating the presence of alternative pathways normally suppressed by Cbl. To further elucidate pre-TCR/TCR signaling pathways involved in thymic development, we characterized the effect of Cbl inactivation on developmental and signaling defects in mice deficient...
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Authors: Chiang, Y. J., Hodes, R. J. Tags: Short communication Source Type: research

NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice
Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3’s anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d–/–) or invariant NKT cells (Jα18–/–) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed seve...
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Authors: Waddell, A., Zhao, J., Cantorna, M. T. Tags: featured content Source Type: research

Sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against RSV in cotton rats
The respiratory syncytial virus (RSV) is responsible for as many as 199000 annual deaths worldwide. Currently, there is no standard treatment for RSV disease and no vaccine. Sendai virus (SeV) is an attractive pediatric vaccine candidate because it elicits robust and long-lasting virus-specific B cell and T cell activities in systemic and mucosal tissues. The virus serves as a gene delivery system as well as a Jennerian vaccine against its close cousin, human parainfluenza virus type 1. Here we describe the testing of a recombinant SeV (SeVRSV-Fs) that expresses an unconstrained, secreted RSV-F protein as a vaccine against...
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Authors: Zhan, X., Slobod, K. S., Jones, B. G., Sealy, R. E., Takimoto, T., Boyd, K., Surman, S., Russell, C. J., Portner, A., Hurwitz, J. L. Tags: Original Research Source Type: research

Lymph formation, composition and circulation: a proteomics perspective
During the last 20 years a deeper understanding of the lymphatic circulatory system, lymph formation and composition has emerged. This review will examine the current knowledge on the organization of the lymphatic vascular tree, the formation of lymph from the extracellular fluid, lymph circulation and the lymph proteomic composition during physiological and pathological conditions. Formation of the lymph fluid is dependent on pressure gradients in the capillary beds and the composition of the endothelial cell glycocalyx, which acts as a molecular sieve. Fluid propulsion toward the draining node is dependent on the intrins...
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Authors: Hansen, K. C., D'Alessandro, A., Clement, C. C., Santambrogio, L. Tags: Invited review Source Type: research

In This Issue
(Source: International Immunology)
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Tags: In This Issue Source Type: research

Table of Contents
(Source: International Immunology)
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Subscriptions
(Source: International Immunology)
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Cover
(Source: International Immunology)
Source: International Immunology - April 22, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Bcl11b prevents the intrathymic development of innate CD8 T cells in a cell intrinsic manner
We examined thymocytes at and after the DP stage in Bcl11b F/S826G CD4cre, Bcl11b F/+ CD4cre and Bcl11b +/S826G mice, carrying the allele that substituted serine for glycine at the position of 826. Here we show that Bcl11b impairment leads to an increase in the population of TCRαβhighCD44highCD122high innate CD8SP thymocytes, together with two different developmental abnormalities: impaired positive and negative selection accompanying a reduction in the number of CD8SP cells, and developmental arrest of NKT cells at multiple steps. The innate CD8SP thymocytes express Eomes and secrete IFN- after stimulation...
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Authors: Hirose, S., Touma, M., Go, R., Katsuragi, Y., Sakuraba, Y., Gondo, Y., Abe, M., Sakimura, K., Mishima, Y., Kominami, R. Tags: Original Research Source Type: research

Endometriotic mesenchymal stem cells exhibit a distinct immune phenotype
We report here that proliferation of PBMCs was less inhibited upon co-culture with ectopic MSCs compared with eutopic MSCs. The findings suggest that ectopic MSCs with increased levels of TLRs, collectins, pro-inflammatory cytokines and markers of migration and angiogenesis exhibit a distinct immune phenotype compared to eutopic MSCs. This distinct phenotype may be responsible for the reduced immunosuppressive property of ectopic MSCs and may be associated with the pathogenesis of endometriosis. (Source: International Immunology)
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Authors: Koippallil Gopalakrishnan Nair, A. R., Pandit, H., Warty, N., Madan, T. Tags: Original Research Source Type: research

Co-culture system of human salivary gland epithelial cells and immune cells from primary Sjogren's syndrome patients: an in vitro approach to study the effects of Rituximab on the activation of the Raf-1/ERK1/2 pathway
This study delineates the signaling pathway involved in RTX-mediated down-regulation of pro-inflammatory factors in a co-culture system of pSS salivary gland epithelial cells (SGEC) with syngeneic pSS B-lymphocytes. In addition, the effects of RTX on the activation of the Raf-1/ERK1/2 pathway in pSS SGEC co-cultured with syngeneic pSS T-lymphocytes were also investigated. This study demonstrated that RTX may interfere with the ERK1/2 pathway in a syngeneic co-culture of pSS SGEC with pSS B-lymphocytes, leading to decreased cytokine production by SGEC. These novel findings reveal that syngeneic co-culture of pSS SGEC with p...
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Authors: Lisi, S., Sisto, M., D'Amore, M., Lofrumento, D. D. Tags: Original Research Source Type: research

CCR8 regulates contact hypersensitivity by restricting cutaneous dendritic cell migration to the draining lymph nodes
In this study, we found that Ccr8 –/– mice developed severer contact hypersensitivity (CHS) responses to 2,4-dinitrofluorobenzene, a murine model of ACD, compared with wild-type mice. T cells from Ccr8 –/– mice showed enhanced proliferative recall responses and Th1 and Th17 cell populations were expanded in these mice. However, CHS responses were similar between SCID mice adoptively transferred with Ccr8 –/– and wild-type T cells, suggesting that CCR8 in T cells is not responsible for the exacerbation of CHS. Notably, skin-resident dendritic cells (DCs), such as Langerhans cells and d...
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Authors: Yabe, R., Shimizu, K., Shimizu, S., Azechi, S., Choi, B.-I., Sudo, K., Kubo, S., Nakae, S., Ishigame, H., Kakuta, S., Iwakura, Y. Tags: featured content Source Type: research

In This Issue
(Source: International Immunology)
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Tags: In This Issue Source Type: research

Table of Contents
(Source: International Immunology)
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Subscriptions
(Source: International Immunology)
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research