T-Cell Memory

CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Janssen, E. M. et al. Nature 421, 852–856 (2003)

Requirement for CD4+ T-cell help in generating functional CD8+ T-cell memory. Shedlock, D. J. & Shen, H. Science 300, 337–339 (2003)

Defective CD8+ T-cell memory following acute infection without CD4+ T-cell help. Sun, J. C. & Bevan, M. J. Science 300, 339–342 (2003)

Understanding how memory responses are generated is crucial if we are to develop improved vaccine strategies. Three recent papers have addressed the issue of whether T-cell help is required for the generation of functional CD8+ memory T cells. For primary CD8+ T-cell responses to certain antigens, CD4+ T cells are required to 'license' antigen-presenting cells (APCs) — thought to be mediated by CD40 signalling — to generate a response. But primary CD8+ T-cell responses to infectious agents do not often require T-cell help, because microbial products provide their own immunostimulatory signals for the direct activation of APCs. These studies now show that CD4+ T-cell help is necessary during the priming phase, but not during the recall response itself, to generate an effective CD8+ memory T-cell response.

Cell Death And Immunity

Essential role for caspase 8 in T-cell mediated homeostasis and T-cell mediated immunity. Salmena, L. et al. Genes Dev. 17, 883–895 (2003)

The role of caspase-8 in immunity is uncertain as disruption of the gene is lethal during embryogenesis. In this new study, mice with a T-cell-specific caspase deficiency were shown to have normal thymic output of T cells but decreased numbers of peripheral T cells. T-cell clonal expansion was also impaired — apparently owing to reduced survival rather than a defect in T-cell activation — and the mice were unable to mount effective anti-viral responses.

T-Cell Activation

ISKAP-55 regulates integrin adhesion and formation of T cell–APC conjugates. Wang, H. et al. Nature Immunol. 4, 366–374 (2003)

A function for the T-cell adaptor protein SKAP55 has long been sought. An initial clue to its role came from previous observations that SKAP55 binds to another T-cell adaptor ADAP, a regulator of integrin clustering. This study shows that similar to APAP, increased expression of SKAP55 in cell lines or primary mouse T cells potently upregulates the formation of T-cell-APC (antigen-presenting cell) conjugates in vitro. It seems that SKAP55 mediates this effect by upregulating integrin clustering and adhesion. So, SKAP55 joins ADAP as a crucial component of the poorly understood 'inside out' signalling pathway that regulates conjugate formation.