Enhancement of proliferation and downregulation of TRAIL expression on CD8(+) T cells by IL-21

Mounting evidence indicates that the cytokine IL-21 can significantly enhance the survival of CD8(+) T lymphocytes. Given that CD4(+) T lymphocytes constitute the main cellular source for IL-21 in vivo, it is tempting to speculate a direct role in mediating the "help" provided by these CD4(+) T cells to the CD8 response. A new report in this issue of the European Journal of Immunology advances this notion by showing that CD8(+) T cells lacking the IL-21 receptor phenocopy those primed in the absence of CD4(+) T cells (the so-called "helpless" CD8(+) T cells) in their induction of the pro-apoptotic factor TRAIL. This finding helps to define the role of IL-21 in the CD8 response, and raises new questions relevant for achieving a broader understanding of this multifunctional cytokine.Tumorimmunolog

The CD4(+) T-cell help signal is transmitted from APC to CD8(+) T-cells via CD27-CD70 interactions

CD8 (+) cytotoxic T lymphocytes are critical components of immunity against infectious pathogens, tumours, and in the case of pathogenic autoimmunity, normal self tissues. CD4 (+) T (T(H)) cells provide ‘help’ to CD8 (+) cytotoxic T lymphocytes during priming by first activating antigen-presenting cells via CD40–CD40L interactions. Here we show that, after immunization with either a noninflammatory, nonreplicating antigen or an overtly inflammatory replicating antigen, CD8 (+) cytotoxic T lymphocytes prevented from receiving a signal through CD27 during priming subsequently exhibit a specific defect in their capacity for secondary expansion that can be rescued by the absence of TRAIL. Thus, the ‘help message’ is transmitted to CD8 (+) T cells via CD70–CD27 signals, enabling them to undergo secondary expansion and avoid TRAIL-mediated apoptosis on re-stimulation. These findings complete our understanding of the cellular interactions through which T(H) is provided to CD8 (+) cytotoxic T lymphocytes during priming

Separate roles for antigen recognition and lymph node inflammation in CD8+ memory T cell formation

Priming of naive CD8(+) T cells by pathogens or vaccines generally involves their interaction with Ag-loaded dendritic cells (DCs) in the context of an inflamed lymph node. Lymph node activation fosters DC and T cell encounters and subsequently provides newly primed T cells with nurturing conditions. We dissected these two aspects by infusing in vitro primed CD8(+) T cells into naive recipient mice harboring a single activated lymph node and comparing the fate of these T cells with those infused into control recipients. Brief (20 h) in vitro priming empowered the T cells to expand in vivo without further Ag stimulation. This primary response was not affected by the presence or absence of a nonspecifically activated lymph node. In contrast, in vivo antigenic challenge after contraction of the primary response resulted in significantly stronger secondary T cell responses in mice harboring activated lymph nodes, demonstrating that the availability of an activated lymph node supported the generation of T cell memory in an Ag-unrelated manner. The presence of an activated lymph node during the expansion and contraction phase of the primary response did not endow T cells with an instructional program for increased survival or secondary expansion, but primarily served to conserve increased numbers of T cells.Tumorimmunolog

Sustained Antibody Responses Depend on CD28 Function in Bone Marrow Resident Plasma Cells

Tumorimmunolog

Sustained Antibody Responses Depend on CD28 Function in Bone Marrow Resident Plasma Cells

Tumorimmunolog