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B Lilliehöök

Publications and source records attributed to B Lilliehöök.

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Search for specific effector functions of C3H X CBA lymphocytes which have proliferated in the spleens of irradiated CBA mice.

Injection of C3H X CBA hybrid lymphocytes into CBA mice specifically reduces the pool of host T cells which are reactive against the Mls antigen determined by the C3H genome. Since C3H X CBA lymphocytes are triggered to cell division in the spleens of irradiated CBA mice we have now examined if such activated cell populations exhibit any effector functions against CBA lymphocytes which are reactive against C3H-determined antigens. It was observed that such 'educated' cell populations were unable to significantly kill CBA lymphocytes which are triggered to cell division in C3H X CBA hosts or CBA lymphocytes which can inhibit proliferation of transplanted C3H X CBA bone marrow cells. Moreover, there was no evidence that such 'educated' cell populations can specifically kill anti-C3H-reactive CBA lymphocytes in vitro or damage CBA bone marrow cells in vivo. Thus, these results do not demonstrate that C3H X CBA lymphocytes acquire any effector functions against CBA T cells which are reactive against C3H-determined antigens.

Animals

F1-hybrid anti-parental-strain reactivity. I. Impaired proliferation of CBA lymphocytes in the spleens of irradiated C3H X CBA mice pretreated with CBA spleen cells.

Previous investigations have indicated that C3H X CBA hybrid lymphocytes can neutralize lymphocytes which are reactive against the C3H-determined Mls antigen when injected into the H-2-compatible strain CBA. In this study we have inoculated C3H X CBA hybrids with CBA spleen cells and 2 weeks later lethally irradiated the mice and injected them with CBA lymphocytes to study their proliferation in the host spleen. Proliferation of lymphocytes from CBA mice, but not from C57Bl mice, was significantly impaired in such hosts, indicating that the hybrids had become immunized against the parental cells. In contrast, such an effect was not detected by treating CBA X C57Bl mice with CBA spleen cells. Humoral antibodies in the C3H X CBA hybrids capable of blocking the response of CBA lymphocytes against C3H X CBA cells could not be detected, indicating that inhibition of lymphocyte proliferation is cell mediated rather than by humoral factors.

Animals

F1-hybrid anti-parental-strain reactivity. II. Proliferation of C3H X CBA hybrid lymphocytes in the spleens of irradiated CBA mice.

Experiments were conducted to explore whether C3H X CBA lymphocytes can react by proliferation when they meet parental CBA spleen cells. MLC tests could not detect such a reaction, but infusion of C3H X CBA lymph node cells into irradiated CBA hosts resulted in rapid cell proliferation in the host's spleen. Such a cell proliferation was also observed after infusion of T-cell-enriched lymph node cell preparations or thymic cells from C3H X CBA donors. Upon transfer to new irradiated mice these proliferating cells continued to proliferate in CBA mice but not in C3H X CBA mice. Further evidence that the injected T-cells were the proliferating emerged from experiments where AKR X CBA lymphocytes were found to proliferate in spleens of irradiated CBA mice and that most of these cells posessed the theta antigen determined by AKR. Proliferation of F1-hybrid lymphocytes in the spleens of its irradiated parental strains was found not to be a general phenomenon and is probably restricted to some Mls-antigen-compatible strain combinations. The possibility that the C3H X CBA hybrid lymphocytes are stimulated to proliferations by CBA lymphocytes reactive against the C3H-determined Mls antigen is discussed.

Animals

Induction of specific unresponsiveness against the C3H M1s=antigen in mice, increase of suppressive capacity of C3H X CBA F1-lymphocytes after sensitization against CBA lymphoid cells.

Injection of adult CBA mice with lymphocytes from C3H X CBA donors leads to a specific reduction of the MLC reactivity of the recipients' lymphocytes. This effect is mediated by a population of F1-lymphocytes which do not seem to possess the relevant MLC-stimulatory M1s-antigen. In this investigation we have shown that injection of C3H X CBA mice with CBA, but not C3H spleen cells enhances the 'tolerogenic' capacity of their thymocytes and lymph node cells. A similar enhancing effect was achieved by 'educating' C3H X CBA lymphocytes in irradiated CBA, but not C3H hosts. The results indicate that C3H X CBA lymphocytes reduce the MLC-reactivity by reacting immunologically against CBA T-cells which possess recognition structures for the relevant M1s antigen. Lymphocytes of C3H X CBA mice can be sensitized against such recognition structures which thus renders them more 'tolerogenic'.

Animals

Influence of an M-locus difference on the cellular and humoral immunological reactivity against H-2 determined antigens of the mouse.

Studies were initiated to determine whether an immune response to the Mls antigen of C3H mice could modify responses of CBA lymphocytes (H-2-compatible) to a foreign H-2 complex. CBA lymphocytes, partially tolerant to the C3H-determined Mls antigen, generated less effector cell activity against C57Bl cells (H-2-incompatible) than lymph node cells from normal CBA donors when infused into irradiated C3H X C57Bl hosts. Effector cell activity was measured as the capacity of the cells in the irradiated spleens to inhibit CBA X C57Bl bone marrow proliferation. In contrast, immunization of CBA mice with C3H X C57Bl cells yielded lower antibody titers against C57Bl cells than immunization with CBA X C57Bl cells. Furthermore, preinjection of CBA mice with C3H X CBA cells strongly reduced the capacity of the animals to produce antibodies against C57Bl cells. Thus, these data support the conclusion that an immune response to a foreign Mls antigen may either enhance or suppress an immune response to H-2-incompatible cells.

Animals

Complex nature of the production of 'effector' cells and their interaction with target cells in the M-antigen system of the mouse.

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.

Animals

Partial tolerant state against H-2 disparate cells. No impaired specific reactivity in MLC, GVH, or antibody production.

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.

Age Factors

Disappearance of specifically mlc-responsive lymphocytes in cba mice injected with cells from the h-2-compatible, m-antigen-incompatible strain c3h.

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.

Animals

Specifically decreased MLC response of lymphocytes from CBA mice injected with cells from the H-2-compatible, M-antigen-incompatible strain C3H. Lack of such effect after injection of H-2-disparate C3H-hybrid cells.

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.

Animals

Antibody response in C3H mice injected with CBA lymphoid cells as detected by membrane immunofluorescent staining.

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.

Animals

Reduced capacity to produce specific 'effector' cells after injection of CBA mice with C3H cells.

Lymphocytes from mice of strain CBA are strongly MLC-responsive to lymphocytes from the H-2-compatible but M-antigen-incompatible strain C3H. This strong reactivity disappears after infusion of CBA mice with C3H lymphocytes. This study shows that the host-versus-graft reactivity (swelling of local lymph node after antigen injection) is specifically reduced after injection of CBA mice with C3H times CBA spleen cells. However, lymphocytes from such mice showed a specifically increased GVH reactivity (inhibition of erythroid cell growth) compared with lymphocytes from unimmunized mice. Lymphocytes from normal CBA mice showed a high proliferative rate in the spleens of irradiated C3H times CBA mice. Such 'educated' cells showed strongly increased specific GVH reactivity. Lymphocytes from CBA mice previously injected with C3H times CBA cells showed reduced capacity to proliferate when injected into irradiated C3H times CBA hybrids and a poor capacity to develop new 'effector' cells reactive against C3H times CBA bone marrow target cells. The results indicate that the presence of specifically 'MLC-responsive' lymphocytes in a lymphoid cell population is a prerequisite of its production of 'effector' cells able to respond in this GVH assay.

Animals