Lymphoid Architecture

Manipulation of lymphoid microenvironments in nonhuman primates by an inhibitor of the lymphotoxin pathway. Gommerman, J. L. et al. J. Clin. Invest. 110, 1359–1369 (2002)

Continuous lymphotoxin (LT) signals are essential for the maintenance of lymphoid architecture and the network of follicular dendritic cells (FDCs). This reticular network has been implicated in the pathogenesis of HIV and prion diseases, as well as certain lymphomas and autoimmune diseases, so is inhibition of LT a potential therapy? Gommerman et al. show that in monkeys treated with human LTβ-receptor–immunoglobulin fusion protein, the FDC networks disappeared within several days and affinity maturation of antibodies was impaired.

Apoptosis

TRAIL/Apo-2 ligand induces primary plasma-cell apoptosis. Ursini-Siegel, J. et al. J. Immunol. 169, 5505–5513 (2002)

At the end of an immune response, most antibody-secreting cells (plasma cells) undergo apoptosis, but the mechanisms that regulate this process are not understood. This study indicates that the death receptor TRAIL might have a specific role in the elimination of plasma cells. Similar to resting and activated B cells, plasma cells were shown to express TRAIL, but only plasma cells were susceptible to ex vivo TRAIL-mediated killing.

Hiv

In vivo dynamics of T-cell activation, proliferation and death in HIV-1 infection: why are CD4+ but not CD8+ T cells depleted? Ribeiro, R. M. et al. Proc. Natl. Acad. Sci. USA 99, 15572–15577 (2002)

Deuterated glucose has been used to compare the dynamics of T-cell turnover between HIV-infected and -uninfected individuals. Here, Ribeiro et al. use a mathematical model, which takes into consideration the fact that only a fraction of T cells are proliferating at any given time, to analyse these data. This study provides insights into the differences between CD4+ and CD8+ T-cell dynamics during HIV-1 infection.

Immunotherapy

Gene therapy for Wiskott Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice. Klein, C. et al. Blood 14 November 2002 (DOI 10.1182/blood-2002-05-1423)

Wiskott-Aldrich syndrome (WAS), an X-linked primary immunodeficiency, is caused by mutations in the WASP gene. This study shows that retroviral transduction of WASP−/− haematopoietic stem cells with WASP can rescue the T-cell signalling defect that is seen in the absence of the protein. These results are encouraging for possible gene-therapy trials for WAS.