Antigen presentation

Granulocyte–macrophage colony-stimulating factor induces an expression program in neonatal microglia that primes them for antigen presentation.Re, F. et al. J. Immunol. 169, 2264–2273 (2002)

Only a subset of microglial cells in the brain are replenished by the migration of monocytes across the blood–brain barrier. In the brain, microglial differentiation is influenced by cytokines released by astrocytes and neurochemicals released by neurons. Macrophage colony-stimulating factor (M-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF) are two cytokines that differentially regulate microglial differentiation. In this study, Re et al. assessed gene expression after stimulation of microglia with M-CSF or GM-CSF. Treatment of primary mouse microglia in vitro with M-CSF induced the expression of genes that function in tissue organization and remodelling, and in brain homeostasis, whereas treatment with GM-CSF induced the expression of genes that prepare microglia for antigen presentation — such as MHC class II molecules, cathepsins and chemokines — and T-cell stimulation.

T-cell responses

Profound defect in T-cell responses in TNF-receptor-associated factor 2 dominant-negative mice.Cannons, J. L. et al. J. Immunol. 169, 2828–2831 (2002)

Tumour-necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is an adaptor protein that links members of the TNFR family, including OX40, CD27 and 4-1BB, to downstream signalling pathways. In this study, the authors used TRAF2 dominant-negative (TRAF2.DN) mice, which had been generated previously, to investigate the role of TRAF2-linked receptors in T-cell responses. TRAF2.DN T cells had impaired responses in mixed lymphocyte reactions. In addition, TRAF2.DN mice had defective CD4+ and CD8+ T-cell responses to influenza virus. These results indicate that TRAF2-linked receptors have an important role in secondary T-cell responses.

T-cell signalling

Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during immunological synapse formation.Dupre, L. et al. Immunity 17, 157–166 (2002)

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency that results from mutations in the Wiskott-Aldrich syndrome protein (WASp). T-cell receptor (TCR) signalling and T-cell proliferation is defective in patients with this syndrome, but the underlying mechanism of these defects is unknown. Dupre et al. now show that within seconds of TCR–CD28 activation, WASp is recruited to lipid rafts in normal T cells. Studies with T cells from WAS patients showed that WASp is required for efficient T-cell proliferation, lipid-raft clustering and upregulation of the lipid-raft marker GM1 at the cell surface after TCR–CD28 stimulation. These data indicate that WASp regulates lipid-raft dynamics during T-cell activation, and thereby immunological-synapse formation.