T-cell dependency of the response to PVP is dependent on maturity of B-cells.
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Biomedical subjects
Publications and source records attributed to H Blomgren.
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The treatment of a case of Hodgkin's disease (lymphocyte predominance, stage IV B) with exogenous i.m. interferon therapy is described. B symptoms disappeared, diseased nodes and pulmonary infiltrations decreased in size, and laboratory values normalized. Clinical improvement was associated with increased mitogenic responsiveness of the patient's lymphocytes towards various stimuli in vitro. After almost half a year's treatment tumour progression and a decreased mitogenic response were again observed. Interferon treatment was then abandoned and combined cytostatic courses were instituted. Partial remission was achieved after 6 months of cytostatic therapy, i.e. 1 year after the start of treatment.
Lymphocytes incubated with antigens or nonspecific stimulatory agents may release factors that induce DNA synthesis in other lymphocytes. The aim of this investigation was to determine whether such mitogenic factors (MF) are produced by both T and B cells in the human. Both T- or B-cell-enriched cell preparations from peripheral blood were found to release MF during or after incubation with phytohemagglutinin or pokeweed mitogen. Concanavalin A covalently bound to Sepharose triggered B-cell preparations to higher MF release than either T cells or unfractionated lymphocyte suspensions. These results strongly indicate that both T and B cells in the human are able to produce MF.
Human peripheral lymphocytes that have been exposed to phytohemagglutinin (PHA) release mitogenic factors (MF) on subsequent incubation in fresh medium. In this investigation, MF-rich supernatants were analyzed for their ability to induce DNA synthesis in various fractions of peripheral human lymphocytes. MF was found to induce higher DNA synthesis in T-cell preparations that in unfractionated lymphoid preparations or B-cell-rich fractions. Evidence is presented showing that some types of non-T-cell can inhibit the MF response of T cells. These cells are nonadherent and nonphagocytic and require DNA synthesis to express their inhibitory activity. These results suggest that the regulation of the action of lymphocyte-derived MF is cell-mediated.
The capacity of lymphocytes from mouse strain CBA to generate 'effector' cells against the H-2-compatible, M-antigen-incompatible strain C3H and their interaction with such target cells were investigated. It was observed that CBA lymphocytes injected in, and 5 days later obtained from, the spleens of irradiated C3H X CBA hybrids ('educated cells') could strongly inhibit the growth of C3H X CBA bone marrow cells but were almost nonresponsive to C3H X C57BI bone marrow targets (H-2-incompatible). CBA lymphocytes educated in irradiated C3H X C57BI hosts displayed reactivity against C3H X C57BI and CBA X C57BL but not against C3H X CBA bone marrow target cells. Additional tests indicated that the M antigen determined by C3H is expressed to approximately the same extent on C3H X CBA and C3H X C75BL cells and that the M antigen on C3H does not cross-react immunologically with antigens on C57BL cells. Moreover, it was observed that CBA X C57BI lymphocytes were triggered to cell proliferation by C3H antigens but were unable or had a highly reduced capacity to develop 'effector' cells in response to this antigenic stimulus. These results indicate that generation of 'effector' cells and their interaction with target cells are very complex processes.
Experiments were conducted to ascertain to what extent the mitogen response of human peripheral T cells is influenced by contaminated, nonresponding leukocytes. T- and B-lymphocyte preparations, extensively depleted of monocytes, exhibited extremely poor responses to pokeweed mitogen and concanavalin A compared with the original unfractionated cell population. A strongly reduced phytohemagglutinin response was noted in the B-cell but not in the T-cell fraction. Mixtures of cell preparations enriched in T or B cells yielded stimulations higher than expected. Mitomycin-C-treated T-cell preparations mixed with untreated preparations enriched in B cells gave slightly higher responses than expected. However, highly enhanced responses were observed when untreated T cells were mixed with mitomycin-treated cell suspensions enriched in B cells. A similar enhancing effect was noted when mitomycin-treated cell suspensions enriched in adherent cells were added. It is concluded that the mitogen reactivity of T cells, on a cell-for-cell basis, may be enhanced tenfold or more by cocultivation with unresponsive non-T leukocytes. A reduced mitogen reactivity of peripheral lymphoid cells from patients with various types of disease may thus either reflect a decreased proportion of responsive lymphocytes or unresponsive non-T lymphocytes capable of enhancing mitogen reactivity, or both.
Injection of CBA mice with H-2-compatible lymphoid cells from C3H hybrids induces a specific reduction of the mixed lymphocyte culture (MLC) response of their lymphoytes. This is not the case after injection of H-2-disparate C3H-hybrid cells, presumably because they are rapidly eliminated due to the immune response of the host. This investigation shows that CBA mice injected with CBA X C57Bl cells (H-2-disparate) at an age of 0-3 days, but not older, develop a specifically reduced MLC response after infusion of C3H X C57Bl cells as adults, indicating that they were tolerant to the C57Bl-determined antigens. However, lymphocytes from such mice showed a normal reactivity against C57Bl as assessed by MLC, graft-versus-host tests, and capacity to produce specific antibodies.
The in vitro mitogen response of blood lymphoid cells from patients with chronic lymphocytic leukemia was observed to be low compared to lymphocytes from healthy subjects. However, highly responsive cells could be separated from the blood of such patients by a buoyant density centrifugation technique and such reactive cells were found to be enriched by treating the patients with chemotherapy or splenic irradiation.
Human lymphocytes were exposed to varying doses of roentgen irradiation in vitro and thereafter tested for reactivity to different polyclonal mitogens and antigens using DNA synthesis as a marker for viability. The dose response profiles obtained indicate that there are two subpopulations of lymphocytes which are responsive to phytohaemagglutinin, poke weed mitogen, concanavalin A and allogeneic cells. One is relatively sensitive to radiation and the other is relatively resistant. However, no "resistant" PPD-tuberculin responsive cell population could be detected. Irradiated lymphocyte populations enriched for T-cells exhibited both a sensitive and a resistant PHA-responsive population, whereas cell populations enriched for B-cells only exhibited a radiation sensitive one.
Thymus-derived and non-thymus-derived peripheral blood lymphocytes were examined by means of E- and EAC-rosette tests. The frequency of these lymphocyte populations was the same in hyperthyroid and euthyroid individuals. It was also demonstrated that PHA responsiveness of lymphocytes from hyperthyroid patients was equal to that of lymphocytes from euthyroid controls and did not change after treatment with 131I.
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The mixed lymphocyte culture (MLC) response of lymphocytes from CBA mice injected with spleen cells from the H-2-compatible strain C3H was studied. The response of CBA lymphocytes against C3H cells was higher than that obtained against H-2-disparate strains. Intravenous injection of C3H cells resulted in a markedly increased MLC response in lymph nodes but not in the thymus during the first 1 to 3 days. Thereafter, the specific MLC response decreased drastically, far below that of nonimmunized animals. Reactivity was back to normal in the thymus after approximately 4 weeks but remained suppressed in lymph nodes for more than half a year. A decreased response was also noted in spleen, Peyer's patches, and the peripheral blood lymphocyte population. Such a state of relative unresponsiveness was achieved by injecting as few as 10-4 C3H spleen cells. This exhaustion of the specific MLC response could not be explained by production of blocking serum factors or of cells that can inhibit the MLC response. The strong MLC response obtained by lymphocytes from nonimmunized animals may be due to disparity at the newly detected M locus. This antigenic system is characterized by strong MLC stimulatory capacity and no detectable production of humoral antibodies or development of effector cells capable of killing M-antigen-bearing cells. A possible explanation of the results is that the CBA mice become chimaeric for a long time after injection of C3H cells. This prolonged exposure to a foreign transplantation antigen may lead to exhaustion of the specifically responsive lymphocytes.
The mixed lymphocyte culture (MLC) response of lymphocytes from CBA mice against C3H cells was studied after injection of spleen cells from C3H mice or C3H hybrids. Intravenous infusion of C3H cells resulted in a strongly suppressed specific MLC response, but this was not the case when cells from H-2-incompatible hybrids of C3H mice were injected. However, when mixtures of cells from the two parental strains--C3H cells and H-2-incompatible cells--were injected into CBA mice, there was a strongly suppressed MLC response to C3H cells. Mice that were hybrids between CBA and an H-2-disparate strain showed a depressed MLC response against C3H after injection of cells from hybrids between C3H and the same H-2-disparate strain. The results may indicate that a suppression of the MLC response to the strongly stimulatory non-H-2 antigen on C3H lymphocytes develops only when the immunizing cells can survive in the host for long periods, thus exhausting the pool of specifically responsive cells. The presence of another foreign transplantation antigen, such as H-2, on the same cells shortens the survival of the cells in the recipient.
Lymphocytes from CBA mice are strongly responsive to cells from the H-2-identical strain C3H in vitro (MLC), whereas C3H lymphocytes are poorly reactive against CBA cells. Immunization of CBA mice with C3H lymphocytes did not yield any detectable specific antibodies. On the other hand, C3H mice immunized with CBA cells produced specific antibodies as detected by membrane immunofluorescence. Mice of the strains AKR and DBA/2 also possess this specific membrane alloantigen. We thus conclude that it is now possible to discriminate among lymphocytes of CBA and C3H origin.