IntroductionThere is now clear evidence that CD4 ϩ T cells contain a population of naturally immunosuppressive T cells characterized by constitutive expression of CD25, CTLA-4, and FOXP3. 1 Because not all potentially autoreactive T cells are deleted in the thymus, 2,3 peripheral control of T-cell responses by naturally occurring CD4 ϩ CD25 ϩ FOXP3 ϩ immunoregulatory T cells (T regs ) is crucial to prevent autoimmunity. 1 Depletion of T regs contributes to the induction of severe autoimmune diseases in animal models, and several studies have reported a defect of T regs in various human autoimmune diseases. 1,4,5 Despite extensive research to unravel the immunosuppressive function of T reg , the exact molecular mechanism of immunosuppression is still elusive. Promising targets for pharmacologic mimicking of T regs function remain undefined. Consequently, direct use of T regs for therapy is currently under examination. Therapeutic expansion or depletion of T regs with defined antigen specificity offers new treatment options for human diseases. 6 Because accumulation of T regs has been shown to be detrimental in cancer, 7 new insights into mechanisms of T reg homeostastis are required.To gain new insight into the modulation of T reg numbers as well as their antigen specificity, the development of natural T regs during ontogeny and in the adult needs to be explored. The peripheral T reg compartment consists mainly of thymus-derived T regs . 1 However, under specific circumstances T regs can also be generated out of conventional T cells (T convs ) (eg, if the antigen is targeted to immature dendritic cells [DCs]). [8][9][10] It has yet to be established how much "converted" T regs contribute to the total number of T regs in the periphery of adult mice and humans.At a given time, the overall number of T regs is defined by a balance of generation and demise of T regs . At the end of an immune reaction, T cells are depleted by apoptosis. Activation-induced cell death (AICD) through CD95/CD95L has been described as such an apoptosis-inducing mechanism. 11 While naive T cells are CD95 Ϫ and resistant to apoptosis induction, activated T cells (CD45RO hi ) up-regulate CD95 and become sensitive to apoptosis. Upon T-cell receptor (TCR) restimulation, activated effector T cells (T effs ) up-regulate CD95L and induce AICD through crosslinking of CD95 by CD95L. AICD eliminates T effs after an immune response and contributes to T-cell homeostasis. We have previously shown that most T regs constitutively express CD95 and can easily be killed via crosslinking of this death receptor by CD95L. 12 Together with the fact that most T regs express high levels of CD45RO, we contributed expertise in microarray analysis; J.P. contributed clinical samples; P.K. analyzed data and assisted in writing the paper; O.L. contributed clinical samples and assisted in writing the paper; and E.S.-P. designed research and wrote the paper.The online version of this article contains a data supplement. For personal use only. on April 5, 2019. by guest www....

L‐selectin belongs to the C‐type lectin family of glycoproteins and is constitutively expressed on most leukocytes. L‐selectin mediates leukocyte rolling in inflamed microvessels and high endothelial venules (HEV) via binding to specific carbohydrate structures on selectin ligands. Previous studies using sialidase treatment suggested a role of sialic acid residues in L‐selectin‐dependent rolling. To investigate the role of the α2,3‐sialyltransferase (ST3Gal)‐IV on L‐selectin ligand activity in vivo, we studied leukocyte rolling in inflamed venules of the cremaster muscle and in Peyer's patch HEV of ST3Gal‐IV‐deficient mice and littermate control mice. In cremaster muscle venules with or without TNF‐α treatment, L‐selectin‐dependent rolling was almost completely abolished in ST3Gal‐IV–/– mice. In both models, L‐selectin interacts with P‐selectin glycoprotein ligand‐1 (PSGL‐1) presented by adherent leukocytes and leukocyte fragments, but not with endothelial L‐selectin ligands. In contrast, L‐selectin‐dependent rolling in Peyer's patch HEV, which is mediated by unknown endothelial L‐selectin ligands, was not impaired in the absence of ST3Gal‐IV. Our in vivo data show that PSGL‐1, the molecule responsible for L‐selectin‐mediated leukocyte interactions in inflammation, is dependent on ST3Gal‐IV, while α2,3‐sialylation by ST3Gal‐IV is not necessary for L‐selectin ligand activity on high endothelial cells of Peyer's patch HEV.

Incontinentia pigmenti (IP) is a rare neurocutaneous disorder caused by mutations in the NEMO (NF-ĸB essential modulator) gene. Skin lesions are typically the first manifestation of IP though they may be accompanied by multiple malformations. This report presents the case of a female newborn with early onset of IP lesions within the 1st day of life. After the age of 1 month she developed frequent episodes of severe gastroenteritis. Examination of the immune system revealed low concentrations of IgG subclasses. This study suggests that, contrary to previous belief, IP is associated with immune deficiency.