Effect of activated lymphocytes on the regulation of hematopoiesis: enhancement and suppression of in vitro BFU-E growth by T cells stimulated by autologous non-T cells

Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.     

Hair follicles serve as local reservoirs of skin mast cell precursors

Several leukocyte populations normally reside in mouse skin, including Langerhans cells and gammadelta T cells in the epidermis and macrophage and mast cells in the dermis. Interestingly, these skin resident leukocytes are frequently identified within or around hair follicles (HFs), which are known to contain stem cell populations that can generate the epidermal architecture or give rise to the melanocyte lineage. Thus, we reasoned that HFs might serve as a local reservoir of the resident leukocyte populations in the skin. When vibrissal follicles of adult mice were cultured in the presence of stem cell factor (SCF), interleukin 3 (IL-3), IL-7, granulocyte-macrophage colony-stimulating factor, and Flt3 ligand, CD45+/lineage-/c-kit+/FcepsilonRI+ cells became detectable on the outgrowing fibroblasts in 10 days and expanded progressively thereafter. These HF-derived leukocytes showed characteristic features of connective tissue-type mast cells, including proliferative responsiveness to SCF, metachromatic granules, mRNA expression for mast cell proteases-1, -4, -5, and -6, and histamine release on ligation of surface IgE or stimulation with substance P or compound 48/80. These results, together with our findings that HFs contain c-kit+ cells and produce SCF mRNA and protein, suggest that HFs provide a unique microenvironment for local development of mast cells.     

Hematopoietic progenitor cells from allogeneic bone marrow transplant donors circulate in the very early post-transplant period

Despite the therapeutic efficacy of allogeneic bone marrow transplantation (allo-BMT), circulating hematopoietic progenitor cells after bone marrow transplantation have not been well characterized. In the present study, we focused on these 'post-transplant circulating progenitor cells (PTCPC)' which may be on their way to bone marrow. We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just before transplantation), 1 (8-15 h after the completion of transplantation), 2, 3, 5, 7, 10, 14, 17, 21, 28 and 35 after allo-BMT in five transplant patients using a standard methylcellulose assay. In addition, high proliferative potential colony-forming cells (HPP-CFC) of the harvested donor bone marrow (BM) and day 1 PB of recipients were assayed in five patients. The origin of HPP-CFC from day 1 PB was analyzed by polymerase chain reaction of a DNA region containing a variable number of tandem repeats. The replating potential of these HPP-CFC was evaluated by a secondary colony assay. The proportion of CD38negative cells among CD34+ cells in the harvested BM and day 1 PB was evaluated by two-color flow cytometric analysis. The number of CFU-GM on day 1 ranged from 6 to 73/10 ml PB, and became undetectable on day 5. The reappearance of PTCPC was observed on day 14, along with hematopoietic recovery. The proportion of HPP-CFC among myeloid colonies from day 1 PB was significantly higher than that from harvested BM (44.3+/-10.4% vs 11.3+/-2.1%, respectively, n=5, P=0.0030). These HPP-CFC from day 1 PB were confirmed to be of donor origin. More than 90% of these HPP-CFC had replating potential. Two-color flow cytometric analysis revealed that the proportion of CD34+CD38negative cells was significantly higher in day 1 PB than in the harvested BM (61.0+/-16.5% vs 9.3+/-3.5%, respectively, n=7, P=0.0002). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following allo-BMT.     

Reversal of dialysis-dependent renal failure in patients with advanced multiple myeloma: single institutional experiences over 8 years

Acute renal failure in patients with multiple myeloma (MM) requiring dialysis is a serious complication and is associated with extremely poor survival. In addition, its treatment included high-dose dexamethasone and/or thalidomide-containing regimens on the reversibility of renal function, which has not been adequately evaluated previously. We studied the impact on the reversibility of high-dose dexamethasone and/or thalidomide-containing regimen in 12 newly diagnosed MM patients (median 74 years, range; 63–85 years) who required dialysis at Kameda General Hospital from 2001 to 2008. There were seven light chain only myelomas, three IgD myelomas, and two IgG myelomas. Ten patients initially received high-dose dexamethasone-based treatment and two received thalidomide-based treatment, with modifications. Complete (CR) and partial responses (PR) were obtained in three and five patients, respectively. Dialysis independency was achieved in all eight patients (67%) who achieved better than PR, with a median duration of 2.0 months. Six of the ten patients who received high-dose dexamethasone-containing regimen and all of the two patients received thalidomide-containing regimen became dialysis-independent. A high concentration of serum-free light chain was detected in all patients examined, before the start of anti-myeloma treatment, and this was associated with the presence of advanced renal failure. Improved renal function was preceded by a significant decrease in serum-free light chain in patients who achieved dialysis independence. These results suggest that dialysis-dependent renal failure is reversible by dexamethasone- or thalidomide-based treatments in most patients with MM, even if the patient is in advanced age, and that serum-free light chain monitoring might be useful for predicting improvements in renal function.     

Primary amyloidosis associated with IgD-lambda M-proteinemia

We describe here a case of primary AL amyloidosis associated with IgD monoclonal gammopathy of undetermined significance. A 73-year-old man was referred to our hospital with suspected multiple myeloma due to renal failure and urinary Bence Jones protein. Although serum electrophoresis revealed IgDlambda monoclonal protein, the bone marrow did not showed plasma cell proliferation. Systemic bone survey disclosed no lytic bone lesions. Because the patient had macroglossia and multiple ecchymosis in the face and neck, primary amyloidosis was suspected. Skin biopsy revealed extensive deposition of amyloid which was positively stained by Congo red dye. A diagnosis of primary AL amyloidosis associated with IgD monoclonal gammopathy was made. The patient was also complicated renal failure that eventually needed hemodialysis. To our knowledge, this is the first report of primary AL amyloidosis associated with IgD monoclonal gammopathy with undetermined significance.