Nature Immunology pp 1093 - 1101 and pp 1102 - 1110

T cell responses must be finely balanced to avoid inflammatory tissue injury when fighting infection. In the November issue of Nature Immunology, scientists show that Tim-3, a molecule expressed by T_H1 subset, is intimately involved in regulating this balance.

Three groups have now found that the lipid leukotriene B4 (LTB4) is a major mediator of the migration of 'effector' T cells. The recruitment of CD4⁺ and CD8⁺ effector T cells to the inflamed site early in the response requires LTB4. This lipid is most likely released by activated mast cells (one of the 'sentinel cells' of the tissue's early warning system) and other leukocytes that reside in the inflamed tissues. Although further work will be required to establish the applicability of these findings to clinical settings, pharmacological inhibition of LTB4 could prove useful for inhibiting recruitment of pathogenic effector cells in inflammatory diseases.

Nature Immunology pp 1065 - 1073

How viruses trigger an immune response has been an enduring enigma. In the November issue of Nature Immunology, scientists show that the ability of specialized immune cells to pick up viral particles from their surroundings and use them to alert other immune cells is an important element in fighting viral infections.

Scientists have known for some time that MHC class I proteins alert the immune system to the presence of virus particles, so that an antiviral response can be triggered. However, it is unclear whether the cells that bear MHC class I proteins on their cell surfaces need to be infected by the virus to send out an alarm, or whether they primarily acquire virus particles from the surrounding tissue during an infection. Jefferies and colleagues from the University of British Columbia, Canada modified the intracellular travels of MHC class I, so that it cannot pick up bits of virus swallowed by the immune cell, and yet it retains the ability to pick up virus if the cell itself is infected. Mice with these modified MHC proteins are crippled in their ability to clear infections. This finding is important in understanding immune responses during viral infections, and also bears on tumor immunity and autoimmune diseases.

Nature Immunology pp 1111 - 1120

Individuals with Hermansky-Pudlak syndrome type 2 (HPS2) are albinos with prolonged bleeding times and increased susceptibility to infections. Patients with HPS2 have mutations in a protein called AP-3, which is involved in directing the movement of proteins inside cells. How mutations in this protein lead to immunodeficiency, however, is unclear. In the November issue of Nature Immunology, scientists show that AP-3 is required by T cells to kill infected cells.

Gillian Griffiths and colleagues from Oxford University found that AP-3—deficient T cells taken from a patient with HSP-2 could not kill target cells. Closer analysis showed that lytic granules, which are required for killing, fail to move towards the contact site between the T cell and target cell. AP-3 therefore appears to be involved in mediating granule movement inside killer T cells.