Autoimmunity

Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. McQualter, J.L. et al. J. Exp. Med. 194, 873?882 (2001)

The chronic autoimmune demyelinating disease mutliple sclerosis (MS) is characterized by an inflammatory infiltration of immune cells into the central nervous system (CNS). Immunization of mice with myelin proteins results in a similar disease, experimental autoimmune encephalomyelytis (EAE), and provides a useful animal model. The cytokine granulocyte macrophage colony-stimulating factor is implicated in chronic inflammation, leading the authors to investigate whether this might be a therapeutic target in MS. GM-CSF−/− mice were found to be resistant to the induction of EAE and, importantly, immune cells failed to infiltrate the CNS.

T-cell signalling

Single-cell analysis of signal transduction in CD4 T cells stimulated by antigen in vivo. Zell, T. et al. Proc. Natl Acad. Sci. USA 98, 10805?10810 (2001)

Lymphocyte signal transduction is commonly analysed in vitro, in bulk populations of transformed cells. However, results are often contradictory. Here, the early signalling events following activation of naive CD4+ T cells was studied in a more physiological ex vivo system. Traceable numbers of naive CD4+ T-cell receptor transgenic T cells were transferred into normal mice, which were then challenged with specific antigen. At various time points, lymphoid tissues were removed, fixed immediately and then phosphorylation of key signalling molecules was measured by flow cytometry. In contrast with previous in vitro studies, this analysis indicates that phosphorylation of c-jun and p38 mitogen-activated protein kinase does not depend on co-stimulatory signals from CD28.

Allergy

Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Jutel, M. et al. Nature 413, 420?425 (2001)

Specialized subsets of T helper cells (TH1 and TH2) are present at sites of inflammation where effector cells, including mast cells and basophils, produce mediators such as histamine. In this study, Cezmi Akdis' group show that histamine can regulate inflammatory reactions by enhancing TH1-type responses through the histamine receptor type 1 (H1R). Conversely, TH1-and TH2-type responses are both negatively regulated through the H2R. Secretion of interferon-γ was suppressed in H1R knockout mice, and TH2 cytokines (IL-4 and IL-13) were predominantly expressed. TH1 and TH2 cytokine expression was upregulated in H2R knockout mice. Interestingly, mice lacking the H1R display increased antibody responses, expressing higher levels of immunoglobulin E (IgE), IgG1, IgG2b and IgG3 in comparison with the H2R-deficient mice. These results show a new immunoregulatory role for the effector mediator histamine.