Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in patients with alpha-1-antitrypsin deficiency.

Granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic stem and progenitor cell (HSPC) mobilization is associated with the release of neutrophil-derived proteases. Previously, we have shown that alpha-1-antitrypsin (AAT) inhibits these proteases in mice, resulting in inhibition of HSPC mobilization. Here, we studied the relationship between AAT and HSPC in steady state and cytokine-induced mobilization in humans.

Local autoantigen expression as essential gatekeeper of memory T-cell recruitment to islet grafts in diabetic hosts.

It is generally believed that inflammatory cues can attract noncognate, "bystander" T-cell specificities to sites of inflammation. We have shown that recruitment of naive and in vitro activated autoreactive CD8⁺ T cells into endogenous islets requires local autoantigen expression. Here, we demonstrate that absence of an autoantigen in syngeneic extrapancreatic islet grafts in diabetic hosts renders the grafts "invisible" to cognate memory (and naive) T cells.

Preservation of recall immunity in anti-CD3-treated recent onset type 1 diabetes patients.

Background: The safety of any immune modulating agent in type 1 diabetes mellitus (T1DM) involves its selectivity on autoimmunity and its preservation of recall and tumour immunity.

Methods: We performed lymphocyte proliferation tests on seven recent onset diabetic patients treated with anti-CD3 (Otelixizumab; ChAglyCD3) and five recent onset diabetic patients treated with placebo, on average 2 years after therapy.

Results: Proliferative responses towards common viral, bacterial and yeast antigens upon in vitro stimulation with a range of recall antigens in anti-CD3-treated T1DM patients were highly similar to those in placebo-treated T1DM patients.

Development and application of fully functional epitope-tagged forms of transforming growth factor-beta.

Administration of transforming growth factor-beta (TGF-beta) has been found to be of therapeutic benefit in various mouse disease models and has potential clinical usefulness. However, the ability to track the distribution of exogenously administered, recombinant forms of these proteins has been restricted by cross-reactivity with endogenous TGF-beta and related TGF-beta isoforms. We describe novel FLAG- and hemagglutinin (HA)-tagged versions of mature TGF-beta1 that retain full biological activity as demonstrated by their ability to inhibit the growth of Mv1Lu epithelial cells, and to induce phosphorylation of the TGF-beta signaling intermediate, smad 2.