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Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G...
Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo recombination in CD4 − CD8 − (double negative DN) and CD4 + CD8 + (double positive DP) thymocytes, respectively. TcraTcrd locus variable gene segments are subject to complex regulation. Only a small subset of...
IL-4 receptor (IL-4R)-deficient CD8+ T cells specific for the circumsporozoite protein of Plasmodium yoelii develop a severely impaired memory response after priming with parasites. Memory CD8 + T cells lacking the IL-4R are unable to establish a stable population residing in nonlymphoid organs,...
A long-standing paradox in the study of T cell antigen recognition is that of the high specificity–low affinity T cell receptor (TCR)–major histocompatibility complex peptide (MHCp) interaction. The existence of multivalent TCRs could resolve this paradox because they can simultaneously...
Differentiation of B cells into plasma cells requires X-box binding protein–1 (XBP-1). In the absence of XBP-1, B cells develop normally, but very little immunoglobulin is secreted. XBP-1 controls the expression of a large set of genes whose products participate in expansion of the endoplasmic...
Class switch recombination (CSR) occurs by an intrachromosomal deletion whereby the IgM constant region gene (C μ ) is replaced by a downstream constant region gene. This unique recombination event involves formation of double-strand breaks (DSBs) in immunoglobulin switch (S) regions, and...
The enzyme 11 β –hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11 β -HSD1 has a therapeutic effect in mouse models of...
The cytokine thymic stromal lymphopoietin (TSLP) has recently been implicated in the pathogenesis of atopic dermatitis (AD) and other allergic diseases in humans. To further characterize its role in this disease process, transgenic mice were generated that express a keratinocyte-specific,...
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