Innate Immunity

Innate immunity in Arabidopsis thaliana : lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes. Zeidler, D. et al. Proc. Natl Acad. Sci. USA 101, 15811–15816 (2004).

The recognition of pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), by Toll-like receptors is a key feature of innate immunity in vertebrates and insects. Plants can also respond to LPS, and the authors show that, similar to animal responses, this can result in the production of nitric oxide (NO). Exposure of Arabidopsis thaliana cells to LPS led to a rapid burst of NO production through the action of the NO synthase AtNOS1. This induced expression of an array of defence or stress-associated genes. A. thaliana plants lacking AtNOS1 developed disease faster and had more-severe symptoms after exposure to a bacterial pathogen. So, NO production in response to PAMPs seems to be a highly conserved immune-defence mechanism.

Regulatory T Cells

Role of LAG-3 in regulatory T cells. Huang, C.-T. et al. Immunity 21, 503–513 (2004).

To harness the therapeutic potential of regulatory T (TReg) cells, they need to be easily identified on the basis of cell-surface marker expression. This paper identifies the CD4-related, MHC-class-II-binding molecule LAG3 as a phenotypic marker of both natural and induced TReg cells that also has a role in their functional activity. LAG3 is highly expressed by TReg cells compared with antigen-activated effector CD4+ T cells, and this is in contrast to other suggested markers of TReg cells such as CD25, GITR and CTLA4, which can be upregulated by activated effector T cells. Deficiency in LAG3 prevents regulatory activity, whereas forced expression of LAG3 induces suppressor activity. The regulatory mechanism of LAG3 remains to be determined, and Lag3-knockout mice are being studied for evidence of autoimmune defects.

Evolution

Resolution of the novel immune-type receptor gene cluster in zebrafish. Yoder, J. A. et al. Proc. Natl Acad. Sci. USA 101, 15706–15711 (2004).

Previous studies have identified four families of novel immune-type receptor (NITR) genes in zebrafish. In this paper, an additional eight NITR gene families were identified in the same cluster. nitr9 encodes a protein with a positively charged amino-acid residue in its transmembrane domain (a characteristic of activating natural-killer-cell receptors), and indeed, it was shown to have activating-receptor function. In addition, the variable domain of NITRs contains three hypervariable regions, the first and third of which are in positions that correspond to complementarity-determining region 1 (CDR1) and CDR3 in the immunoglobulin and T-cell-receptor variable domains. So, studying these molecules could lead to a greater understanding of the evolutionary transition between immunoreceptor recognition of self-receptors and of peptide-loaded self-receptors.