Apoptosis of cells must be managed both positively and negatively in response to various environmental stresses via differential signal transduction cascades. Recently, an apoptosis inhibitor expressed by macrophages (AIM) was presented as a novel murine soluble protein. AIM is a member of the macrophage scavenger receptor, cysteine-rich domain superfamily (SRCR-SF), which shares a highly homologous-conserved, cysteine-rich domain. AIM inhibits the apoptosis of CD4+CD8+ (CD4/CD8) double-positive (DP) thymocytes, and supports the viability of these cells in T cell development in the thymus. In inflammatory sites outside the thymus, AIM appears to enhance macrophage phagocytosis, inhibit B cell proliferation in combination with transforming growth factor-β and inhibit apoptosis of natural killer T (NKT) and natural killer (NK) cells. AIM thus has diverse functions that depend on the type of target cell and its combination with other cytokines.
We previously observed Langerhans cells (LC) in the squamous metaplastic urinary bladder in rats fed a vitamin A-deficient diet. Here we report the finding of LC in the iliac lymph nodes, one of the abdominal lymph nodes draining to the urinary bladder. LC had previously only been observed in the superficial and hilar lymph nodes, but never in the abdominal lymph nodes. This is also the first observation of Birbeck granule (BG)-positive LC in the iliac lymph nodes. LC were not found in the transitional mucosa of the urinary bladder. In the present experiments, the LC were observed in both the squamous metaplastic mucosa and lamina propria of the urinary bladder, and also in the iliac lymph nodes, which drain into the urinary bladder. BG-positive LC may mature not only in the squamous epithelia, but also in squamous metaplastic mucosa. LC in the lamina propria of the urinary bladder might migrate to the iliac lymph nodes, which are regional lymph nodes, where they could function in antigen presentation. LC in the skin play a role in antigen-antibody interactions, and the squamous metaplastic mucosa of the urinary bladder may be a similar environment, in which LC in the mucosa can migrate to the regional lymph nodes.
Dendritic cells (DC) are essential antigen-presenting cells (APC) with a unique capacity to initiate an immune response. We described the in vitro generation of rabbit monocyte-derived DC (Mo-DC) in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4. Autologous DC, which had phagocytosed apoptotic Ra-1 cells, acted as an APC for cellular response following their injection into human T lymphotropic virus type I (HTLV-I)-infected rabbits. PKH-26 labeled DC preferentially homed to the T cell area of the draining lymph node following s. c. injection, whereas i. v. -injected DC accumulated in the spleen. We demonstrated that rabbit Mo-DC functioned as potent APC in vivo and that the route of DC administration was inconsequential for cytotoxic T lymphocytes response. Although Mo-DC generated from patients with adult T-cell leukemia/lymphoma (ATLL) show a functional impairment, this study provides evidence that a new, supporting immunotherapy using the donor's DC generates a more efficient anti-HTLV-I infected cell/ATLL cell immune response following allogeneic stem cell transplantation.
T cell subsets that responded to a superantigen, staphylococcal enterotoxin-B (SEB), were analyzed using responder cells stained with carboxyfluorescein diacetate succinimidyl ester (CFSE). It was shown that T cells dividing 5 times represented the major population 4 days after stimulation with SEB. When the proportion of each T cell subset was analyzed sequentially, Vβ8+ T cells that represented the SEB-responding repertoire increased and reached more than 20% of viable cells 4 days after culture with SEB. Both CD4+ and CD8+ T cells in the Vβ8+ population showed similar increases. By contrast, the proportion of SEB-non-reactive Vβ6+ Tcells showed no considerable increases. The Vβ6+ T cells exhibited prominent apoptosis from an early phase in the culture, whereas Vβ8+ T cells showed activation-induced cell death at the later stage. However, the proportion of dividing cells (CFSElow) in living cells increased substantially in every T cell subset, including NK-T cells, suggesting that a bystander cell proliferation effect was involved. T cells stimulated with SEB produced both Th1 and Th2 type cytokines, although production of each cytokine followed different time courses.
Mucosa-associated lymphoid tissue (MALT) lymphomas usually arise from acquired MALT induced by chronic inflammation or autoimmune processes. In MALT of the gastrointestinal tract lymphocyte homing mechanisms operate primarily through interactions between integrin, expressed on mucosal lymphocytes, and MAdCAM-1, expressed on endothelium of high endothelial venules (HEV). In the present study, the expression of MAdCAM-1 and peripheral lymph node vascular addressin (PNAd) was examined immunohistochemically in normal, inflamed and MALT lymphoma tissues of various organs. It was shown that MAdCAM-1 was expressed on HEV in the gastrointestinal tract and thyroid that are inflamed or affected with MALT lymphomas, but not in the ocular adnexa, lung, and salivary gland. In contrast, PNAd was consistently expressed in all of the inflammatory or lymphomatous lesions examined, but not in the normal tissues. Expression of MAdCAM-1 on HEY may play an important role in lymphocyte migration at sites of chronic inflammation or MALT lymphoma of the gastrointestinal tract and thyroid. In other organs, PNAd may have the greater role.