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

Evidence for a functional second thymus in mice. Terszowski, G. et al. Science 2 March 2006 (doi: 10.1126/science.1123497)

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.