(a) The expression of CD27 and T-cell receptor (TCR) – on splenocytes from or or versus that secreted from mouse was also shown to develop autoimmune diseases in exocrine organs, such as lacrimal gland, lung, liver and salivary glands

(a) The expression of CD27 and T-cell receptor (TCR) – on splenocytes from or or versus that secreted from mouse was also shown to develop autoimmune diseases in exocrine organs, such as lacrimal gland, lung, liver and salivary glands.30 Hence, in the mouse, immune responses to foreign antigens seem to be impaired whereas those to autoantigens are more prone to be invoked compared with WT mouse. proportion of CD8low+ idiotypehigh+ cells, which are thought to potentially represent the lineage of T cells, was markedly decreased. When the T cells in non-transgenic mice were investigated, the proportion of T cells in the peripheral organs of mice was found to be one-half to one-fifth of those in roles have been investigated mainly AIM-100 using an NIK-deficient mouse11 and a spontaneous mutant mouse, alymphoplasia (thymocytes,15 suggesting that NIK plays mandatory roles in TCR-mediated NF-B activation in thymocytes. These results also suggested a possibility that the NIK in thymocytes may be involved in thymic selection, and so in AIM-100 peripheral T-cell repertoire formation. In mice, however, apparent abnormalities have not been found in T-cell development.12 The numbers of thymocytes or splenic T cells in mice are normal, and the peripheral CD4+/CD8+ ratio is almost the same as that in wild-type (WT) mice. Nevertheless, it is still possible that the threshold of positive or negative selection may be shifted by the mutation, and that the mature T-cell repertoire in mice may be different from that in WT mice. In such a case, the analyses should be performed with a fixed TCR, using TCR transgenic (Tg) mice, to follow the fate of the T cells expressing a particular TCR. In contrast to the T cells, information on the role of NIK or of NF-B activation in the development of another subset of T cells, T cells, is sparse. Although the genetic requirements in the development differ between and T cells,16 it is thought that, like T cells, TCR signalling may be crucial for the maturation of (at least some populations of) T cells in the thymus.17 Intriguingly, differentiation of thymic T cells has been shown to be affected by the lymphotoxin (LT) signalling upon interaction with DP T cells.18 Given that NIK is critical in the signal transduction from LT receptor Comp (LTR),11 it appears quite possible that NIK may play some key roles in the development of T AIM-100 cells, which still remain to be explored. In the present study, development of T cells and T cells in mice have been investigated using the TCR- Tg mouse, to reveal the roles of NIK in the development of and T cells. The results suggested that the efficiency of the positive selection of at least some of T cells could be affected by the lack of functional NIK. It was also suggested that peripheral maintenance and/or the development of T cells may require functional NIK to be expressed in non-haematopoietic cells. Materials and methods Mice C57BL/6J (H-2b), DBA/1 (H-2q), C3H/HeN (H-2k) mice were purchased from Charles River Japan, Inc. (Kanagawa, Japan). B10.S (H-2s) mice were purchased from Japan SLC, Inc. (Shizuoka, Japan). The alymphoplasia mice were obtained from Clea Japan, Inc. (Tokyo, Japan), and were bred onto C57BL/6J ?10 times before inter-breeding to produce the mouse or breeding with other strains of mice. The QM11TCR-Tg mouse, possessing the transgenes for the and chains of TCR recognizing AIM-100 I-Ak as the allo-antigen, was described previously.19 In some experiments, analyses were performed using QM11TCR-Tg mice with RAG-2-deficient background.19 The green fluorescent protein (GFP) -Tg mouse of C57BL/6 background [C57BL/6 TgN (act-EGFP) OsbY01]20 was kindly provided from Dr Masaru Okabe (Osaka University) and was maintained in our animal facility. All AIM-100 mice used in this study were maintained in a specific pathogen-free facility of Kitasato University School of Medicine. The experimental procedure was approved by the Animal Experimentation and Ethics Committee of the Kitasato University School of Medicine, and all.