Asthma and allergy
Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Meyer, E. H. et al. Proc. Natl Acad. Sci. USA 103, 2782–2787 (2006)
Conventional CD4+ T cells are thought to have an essential role in the pathogenesis of asthma. However, natural killer T (NKT) cells expressing a semi-invariant T-cell receptor (denoted iNKT cells) have been shown to be involved in the development of allergen-induced airway hyper-responsiveness (AHR). Meyer et al. set out to characterize the role of iNKT cells in the development of AHR and found that intranasal administration of an iNKT-cell ligand (either α-galactosylceramide (α-GalCer) or a synthetic version of a glycolipid from some Sphingomonas spp.) induced severe AHR in mice. Induction of AHR required both interleukin-4 (IL-4) and IL-13 but not the presence of conventional CD4+ T cells. The authors therefore suggest that iNKT cells might synergize with conventional CD4+ T cells in the induction of asthma.
Lymphoid organs
While analysing lymphoid tissues in the neck, Terszowski et al. identified structures with lymphoid characteristics that were not lymph nodes. Instead, these tissues had characteristics of the thymus, including a cortico-medullary architecture, the presence of CD4+CD8+ double-positive thymocytes and the expression of genes associated with thymopoiesis (such as recombination-activating gene 1). Transplantation of these cervical thymi into mice lacking a thymus showed that these structures could be colonized by recipient progenitors, could mediate positive and negative selection and could produce a diverse repertoire of T cells able to provide T-cell help in a T-cell-dependent antibody response. Cervical thymi were found in 90% of BALB/c mice analysed and ∼40% of C57BL/6 mice. Therefore, as the authors point out, this study might complicate the interpretation of a large number of previous studies of T-cell function in which the thoracic thymus was removed to eliminate de novo T-cell production.
Technique
Rapid analysis of T-cell selection in vivo using T cell-receptor retrogenic mice. Holst, J. et al. Nature Methods 3, 191–197 (2006)
Vignali and colleagues have developed a way of bypassing the endless rounds of breeding required to generate T-cell receptor (TCR)-transgenic mice, in which all (or most) T cells express the same TCRαβ. By adapting a method previously developed by this group, they made retroviral constructs expressing both TCR chains from a single composite open reading frame. These constructs were then transduced into mouse haematopoietic stem cells before being adoptively transferred to immunodeficient mice. Using this technique, the authors generated several so-called retrogenic mice that expressed previously characterized TCRs. Importantly, T-cell development and function in these retrogenic mice were similar to the corresponding TCR-transgenic strain. This method therefore offers new practical options to researchers studying T-cell development and function.
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In Brief. Nat Rev Immunol 6, 255 (2006). https://doi.org/10.1038/nri1829
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DOI: https://doi.org/10.1038/nri1829