Lymphoid organogenesis

Different cytokines induce surface lymphotoxin-αβ on IL-7 receptor-α cells that differentially engender lymph nodes and Peyer's patches. Yoshida, H. et al. Immunity 17, 823–833 (2002)

The interleukin-7 receptor-α (IL-7Rα)+ 'inducer' cells for Peyer's patch (PP) and lymph node (LN) development are phenotypically similar, and both must be triggered to express lymphotoxin-αβ (LTαβ) for their function. But, there are differences in the molecular requirements for PP and LN development. The development of PPs, but not LNs, requires IL-7, whereas LN development requires signals through RANK ligand (RANKL). This study shows that in Traf6−/− mice, in which RANKL signalling and LN development is blocked, IL-7 can stimulate the expression of LTαβ on LN inducer cells and treatment with soluble IL-7 restores LN formation. This indicates that the inducer cells for LNs and PPs are functionally similar also.

Transplantation

CD4+CD25+ alloantigen-specific immunoregulatory cells that can prevent CD8+ T-cell-mediated graft rejection: implications for anti-CD154 immunotherapy. van Maurik, A. et al. J. Immunol. 169, 5401–5404 (2002)

Blockade of the CD40–CD154 co-stimulatory pathway using CD154-specific antibodies can promote the long-term survival of allografts in animal models, and there is some evidence that this is mediated, in part, by CD4+ regulatory T cells. But, in some situations, anti-CD154 therapy fails owing to the initiation of graft rejection by CD154-independent CD8+ T cells. This study shows that anti-CD154 treatment at the time of transplantation allows the development of CD4+CD25+ regulatory T cells, which, if present in sufficient numbers, can suppress rejection mediated not only by CD4+ T cells, but also by CD8+ T cells. This phenomenon, known as linked unresponsiveness, is an important clinical goal.

Antibody responses

A critical role for IL-21 in regulating immunoglobulin production. Ozaki, K. et al. Science 298, 1630–1633 (2002)

The authors generated IL-21 receptor (IL-21R)-deficient mice and found that although T-cell function was normal in these animals, the levels of IgG1 and IgG2b were reduced and the level of IgE was increased. However, this B-cell-intrinsic defect is less severe than that seen in mice and humans that are deficient for the cytokine-receptor common γ-chain (which is shared by IL-21R), indicating that normal B-cell responses must involve an additional cytokine(s). Mice that were deficient for both IL-21R and IL-4 had markedly impaired production of all antibody isotypes. So, this study shows that co-operation between IL-4 and IL-21 is essential for antibody responses.