Autopathogenic T Helper Cell Type 1 (Th1) and Protective Th2 Clones Differ in Their Recognition of the Autoantigenic Peptide of Myelin Proteolipid Protein

We previously generated a panel of T helper cell 1 (Th1) clones specific for an encephalitogenic peptide of myelin proteolipid protein (PLP) peptide 139–151 (HSLGKWLGHPDKF) that induces experimental autoimmune encephalomyelitis (EAE) upon adoptive transfer. In spite of the differences in their T cell receptor (TCR) gene usage, all these Th1 clones required W144 as the primary and most critical TCR contact residue for the activation. In this study, we determined the TCR contact residues of a panel of Th2/Th0 clones specific for the PLP peptide 139–151 generated either by immunization with the PLP 139–151 peptide with anti– B7-1 antibody or by immunization with an altered peptide Q144. Using alanine-substituted peptide analogues of the native PLP peptide, we show that the Th2 clones have shifted their primary contact residue to the NH2-terminal end of the peptide. These Th2 cells do not show any dependence on the W144, but show a critical requirement for L141/G142 as their major TCR contact residue. Thus, in contrast with the Th1 clones that did not proliferate to A144-substituted peptide, the Th2 clones tolerated a substitution at position 144 and proliferated to A144 peptide. This alternative A144 reactive repertoire appears to have a critical role in the regulation of autoimmune response to PLP 139–151 because preimmunization with A144 to expand the L141/G142-reactive repertoire protects mice from developing EAE induced with the native PLP 139–151 peptide. These data suggest that a balance between two different T cell repertoires specific for same autoantigenic epitope can determine disease phenotype, i.e., resistance or susceptibility to an autoimmune disease

The paradox of being a woman teacher

In this article I follow genealogical lines of analysis in an attempt to map the different discourses and practices that interweave women’s position in education today. I have theorised education as a nexus of created paradoxical spaces, where the female self has attempted to surpass closed boundaries and to question the dichotomy of the feminised private and/or the masculine public. I have also considered the importance of time restrictions upon women’s lives and have paid attention to the multifarious ways these lives are highly structured by specific space/time regulations. The genealogical cartography I have drawn, depicts various positions, where the female self has created parodic unities and temporary coalitions. Finally in tracing exit points that education has offered women, I have considered some of the implications of feminist theories for the subversion of the various dilemmas and dichotomies the female subject has lived through

TIMs: central regulators of immune responses

Exhaustion of T cell responses during chronic viral infections has been observed in both mouse and man and has been attributed to up-regulation of PD-1 on the surface of exhausted T cells. In patients with chronic human HIV infection, T cell exhaustion leads to opportunistic infections associated with AIDS. However, not all the exhausted T cells express PD-1, suggesting that other molecules may be involved in the phenotype. A new study now demonstrates a central role for T cell immunoglobulin and mucin domain–containing protein-3 (TIM-3) in T cell exhaustion during chronic HIV infection and suggests that TIM-3 may be a novel therapeutic target in chronic viral diseases

IL-12– and IL-23–induced T helper cell subsets: birds of the same feather flock together

Traditionally, CD4+ T cells have been separated into two different subsets named T helper (Th)1 and Th2. A new IL-23–driven subset of Th cells called ThIL-17 has now been described. The data suggest that IL-23 plays an important role in the differentiation of autoreactive pathogenic T cells. Whether these IL-23–induced ThIL-17 cells are a unique subset or are related to other Th subsets is discussed

The Effect of In Vitro Digestion on Antioxidant, ACE-Inhibitory and Antimicrobial Potentials of Traditional Serbian White-Brined Cheeses

This study deals with the effect of in vitro digestion on the functional potential of traditional Serbian white-brined cheeses. The total antioxidant capacity, reducing power and iron (II) chelating properties as well as angiotensin-converting enyzme-inhibitory (ACE-inhibitory) and antimicrobial activities of traditional Serbian white-brined cheeses before and after in vitro digestion were assayed. The traditional cheeses had different antioxidant properties as well as different ACE-inhibitory activities. In vitro digestion improved the total antioxidant capacity (8.42-58.56 times) and the reducing power (by 17.90-99.30%) of investigated cheeses, whereas their chelating ability was slightly improved or unaffected after digestion. In vitro digestion reduced the ACE-inhibitory potential of water-soluble protein fractions, and digested water-insoluble fractions were the major source of ACE-inhibitory peptides. The digestates did not exhibit any antibacterial potential, whereas they showed moderate antifungal potential toward selected micromycetes. The best antifungal potential had Svrljig ovine cheese and Homolje cow cheese. The results of this study clearly point to a significant functionality of traditional white-brined cheeses

Identification And Characterization Of A Second Encephalitogenic Determinant Of Myelin Proteolipid Protein (Residues 178-191) For SJL Mice

We previously described a synthetic peptide of myelin proteolipid protein (PLP), peptide 139-151, which induces experimental allergic encephalomyelitis in SJL/J (H-2s) mice. We have now identified an additional determinant, PLP residues 178-191, that is also a potent encephalitogen in this strain. When PLP peptide 178-191 was compared with peptide 139-151 on an equimolar basis, the day of onset of disease induced by PLP 178-191 was earlier, but the incidence, severity, and histologic features were indistinguishable. Lymph node cells from animals immunized with the whole PLP molecule responded to both PLP 178-191 and 139-151, suggesting immunologic codominance of the two epitopes. PLP 178-191 elicited stronger proliferative responses and this may relate to the earlier onset of disease induced with this peptide. Two CD4+, peptide-specific, I-A(s)-restricted T cell lines, selected by stimulation of lymph node cells with either PLP 178-191 or 139-151, were each encephalitogenic in naive syngeneic mice. The presence of multiple encephalitogenic codominant PLP epitopes within a single mouse strain emphasizes the complexity of the immune response to PLP and its potential as a target Ag in autoimmune demyelinating diseases

Estimation of Serpa cheese ripening time using multiple linear regression (MLR) considering rheological, physical and chemical data

Raw ewes’ milk semi-soft cheeses (RESS-cheeses) are important products in Portugal and in several European regions. Creamy texture is an essential attribute of these cheeses, which results from structural properties that are not always well characterized. Here, the structural changes occurring during the ripening period of a traditional RESS-cheese, known as Serpa cheese, were analysed through small amplitude oscillatory shear (SAOS). Rheological data was complemented with other physical and chemical parameters, that were monitored during ripening, in order to estimate Serpa cheese ripening time using multiple linear regression (MLR). Mechanical spectra indicated a relatively strong structure, comparable to a gel, with a low dependence on frequency at the beginning of ripening and a weak structure, comparable to a concentrated suspension, with a crossing point (Ga=Gk) at the left of the graphic and with both moduli highly dependent on frequency, at the end of ripening. Good correlations (P<0.05) were obtained between structural (hardness and storage modulus) and proteolysis indicators. Using a combination of chemical, colour and rheological parameters we were able to obtain a multiple linear regression (MLR) which allows the estimation of Serpa cheese ripening time with an estimation error of 1.7 d (adjusted R2=0.98, P<0.0001)

CD4+CD25−Foxp3− Th1 cells are the source of IL-10–mediated immune suppression in chronic cutaneous leishmaniasis

Nonhealing forms of leishmaniasis in humans are commonly associated with elevated levels of the deactivating cytokine IL-10, and in the mouse, normally chronic infections can be cleared in the absence of IL-10. Using a Leishmania major strain that produces nonhealing dermal lesions in a T helper type 1 (Th1) cell–polarized setting, we have analyzed the cellular sources of IL-10 and their relative contribution to immune suppression. IL-10 was produced by innate cells, as well as CD4+CD25+Foxp3+ and CD4+CD25−Foxp3− T cells in the chronic lesion. Nonetheless, only IL-10 production by antigen-specific CD4+CD25−Foxp3− T cells, the majority of which also produced IFN-γ, was necessary for suppression of acquired immunity in Rag−/− reconstituted mice. Surprisingly, Rag−/− mice reconstituted with naive CD4+ T cells depleted of natural T regulatory cells developed more severe infections, associated with elevated levels of IL-10 and, especially, Th2 cytokines in the site. The data demonstrate that IL-10–producing Th1 cells, activated early in a strong inflammatory setting as a mechanism of feedback control, are the principal mediators of T cell–derived IL-10–dependent immune suppression in a chronic intracellular infection