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At least 19 recordsLinked to original sources
PubMed1984

Idiopathic paraproteinaemia. IV. The role of genetic factors in the development of monoclonal B cell proliferative disorders--a study in the ageing C57BL/KaLwRij and CBA/BrARij mouse radiation chimeras.

Mouse radiation chimeras, employing strains with a low (CBA/BrARij) and a high (C57BL/KaLwRij) frequency of idiopathic paraproteinaemia (IP), were used in a study on genetic influences in the development of IP, a benign B cell monoclonal proliferative disorder. Taking advantage of the different Igh1 allotypic markers between the two strains, the development of IP with increasing age was investigated by agar electrophoresis, immunoelectrophoresis and immunofixation. Four of 18 CBA recipients transplanted with C57BL bone marrow cells were shown to develop IP of the IgG2a isotype and the Igh1b (donor) allotype during their life. In contrast, none of the 23 C57BL recipients of CBA bone marrow developed an IgG2a paraprotein of the Igh1a allotype. However, in three of these 23 chimeras, an IgG2a and Igh1b (recipient) allotype paraprotein appeared with age; two of these mice proved to be reversals at 12 months and one at 15 months of age. The frequencies of homogeneous immunoglobulins of the donor type in the chimeras corresponded roughly to those of normal mice of the donor strain. Histopathological examination excluded a malignant origin of these monoclonal proliferations. These findings support the view that intrinsic cellular genetic factors are of major importance in the development of IP, a benign B cell neoplasia.

Aging↗
PubMed1991

Deletion of self-reactive T cells in the donor-derived T cells but not in the host-derived T cells in fully allogeneic radiation chimeras. Mls-reactive T cells in allogeneic radiation chimeras.

Kinetics of T cells bearing V beta 6 capable of recognizing Mls-1a were examined in the thymus and peripheral lymphoid organs of two allogeneic bone marrow chimeras; AKR/J(H-2k, Thy1.1,Mls-1a)----C3H/He(H-2k, Thy1.2,Mls-1b) and AKR/J----C57BL/6(H-2b,Thy1.2, Mls-1b). Sequential appearance of host- and donor-derived T cells occurred in the thymus and the peripheral lymphoid organs of both AKR----C3H and AKR----B6 chimeras. The first cells to repopulate the thymus were Thy1.2+ host-derived radioresistant cells, which were synchronized in their development. The host-derived cells in thymus of AKR----B6 chimeras differentiate more rapidly than those in AKR----C3H chimeras. An almost complete replacement from host-derived cells to donor-derived cells occurred by day 21 after reconstitution in AKR----C3H and AKR----B6 chimeras. In the donor-derived thymocytes, none of CD4- or CD8-single positive thymocytes expressed high density of V beta 6 in either AKR----C3H or AKR----B6 chimeras, whereas the host-derived thymocytes in AKR----B6 chimeras contained an appreciable number of CD4-single positive thymocytes bearing V beta 6. In the peripheral lymphoid organs, T cells bearing V beta 6 were virtually abolished in Thy1.1+ cell pool of both AKR----C3H and AKR----B6 chimeras. While V beta 6+ T cells of host-origin were detected in the peripheral lymphoid organs in AKR----B6 chimeras. These result indicated that the donor-derived mature T cells showed deletion of V beta 6 in the thymus and the peripheral lymphoid organs in both AKR----C3H and AKR----B6 chimeras, whereas lack of V beta 6 deletion was observed in the host-derived mature T cells in the AKR----B6 chimeras. These results suggested that the host-derived thymocytes may likely to escape undergoing a negative selection against donor-phenotype in the radiation bone marrow chimeras.

Animals↗
PubMed1987

Self-renewal of pulmonary alveolar macrophages: evidence from radiation chimera studies.

Radiation-induced chimeric mice were used to study the origin of pulmonary alveolar macrophages. Unlike in other studies, these radiation chimeras were prepared by using a special fractionated irradiation regimen to minimize the killing of alveolar macrophage colony-forming cells, putative local stem cells. For this study CBA mice with or without T6 chromosome marker were used. Under this experimental condition, the majority of alveolar macrophages in mitosis are of host origin even after 45 weeks. These data suggest that alveolar macrophages are a self-renewing population under normal steady-state conditions.

Animals↗
PubMed1981

Suppressor cells in transplantation tolerance. I. Suppressor cells in the mechanism of tolerance in radiation chimeras.

Histoincompatible-complete radiation chimeras, after resolving acute graft-versus-host disease (GVHD), establish specific tolerance to host and donor alloantigens. This tolerance can be perturbed with immunosuppressive agents and infusions of small numbers of donor-type cells, with infusions of massive numbers of donor-type cells, or with infusions of a small number of donor-type cells, that were sensitized against host antigens prior to transfer. These chimeras possess T lymphocytes in the spleen that specifically suppress donor to host mixed lymphocyte reactions and adoptively transfer suppression of GVHD to secondary hosts. Nylon-wool fractionation of chimeric spleen cells restores the response of chimeric lymphocytes to host alloantigens, suggesting that transplantation tolerance is not attributable to clonal deletion but the activity of nylon-wool-adherent T suppressor spleen cells.

Animals↗
PubMed1976

Immune responsiveness and incidence of reticulum cell sarcoma in long-term syngeneic radiation chimeras.

Long-term syngeneic radiation chimeras displayed a very low incidence of reticulum cell sarcoma as compared with control mice. Immune reactivity of these animals was studied in vivo by anti-dinitrophenyl antibody titer and affinity and in vitro by mitotic responsiveness to phytohemagglutinin, concanavalin A and lipopolysaccharide. Anti-body titer and affinity as well as the response to T lectins were found to be increased in chimeras. These results were attributed to increased function of mature T2 cells, which could explain the reduced incidence of reticulum cell sarcoma in chimeras.

Animals↗
PubMed1976

[Histogenesis of sarcomas, induced by plastic films, in murine radiation chimeras].

Sarcomas were induced in radiation chimeras CBA/CBAT6T6 by subcutaneous implantation of plastic films 13 months after the irradiation and donor bone marrow transplantation. Of the 12 tumours examined, 11 possessed host kariotype and one--donor karyotype. Development of connective tissue cells from the bone marrow precursors presumably played no significant role in the histogenesis of plastic sarcomas.

Animals↗
PubMed1976

Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance.

Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. Chimeras were studied 7 to 46 months after 1200 R total body irradiation and transplantation of marrow from a littermate donor matched at the major histocompatibility complex. An attempt was made to perturb the stable chimeric state by infusion of large numbers (0.6 to 13.7 x 10(8)/kg) of donor peripheral blood lymphocytes into each respective chimera. Two groups were studied: donors in Group A were normal; donors in Group B had been specifically sensitized against minor histocompatibility antigens of the chimera by repeated skin grafts. None of the nine chimeras in Group A developed significant clinical or histologic evidence of graft-vs-host disease (GVHD) after donor lymphocyte infusion. Eight of the 12 chimeras in Group B, however, developed GVHD which was transient in three and fatal in five. The results in Group A are not consistent with classical theories of tolerance, i.e., elimination or inactivation of potentially reactive cell clones, but suggest the presence of an active mechanism suppressing recognition of host antigens by the infused donor lymphocytes and development of GVHD. The results in Group B indicate that this mechanism can be overcome by infusion of sensitized donor cells. In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanisms suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD.

Animals↗
PubMed1986

Self-tolerance and H-2 antigen expression in semi-allogeneic radiation chimeras are controlled by the extrathymic host environment.

Experiments with thymus-grafted radiation chimeras have implicated the H-2 type of the radio-resistant portion of the thymus as determining self for H-2 restricted T-cell responses. (P1 X P2)F1----P1 chimeras, shown to be fully reconstituted with donor haemopoietic cells, have displayed intolerance to P2 H-2 antigens and expressed aberrant levels of P2 H-2 on their spleen cells. We used semi-allogeneic radiation chimeras grafted with fetal thymuses from parental strain donors to compare the relative contributions of the thymus and the extrathymic periphery in determining self-tolerance and in modulating the H-2 phenotype of heterozygous chimeric spleen cells. As analysed by the rosetting titres of anti-H-2 antisera on chimeric spleen cells, by parental skin graft rejection, and by spleen cell anti-parent cytotoxicity after culture with parental stimulators, the decreased expression of non-host parental H-2 antigens was associated with anti-P2 T-cell reactivity, regardless of the H-2 type of the thymus. The donor thymus did not affect tolerance to parental H-2 or cause aberrant expression of H-2 antigens on spleen cells of syngeneic F1----F1 thymus-grafted chimeras.

Animals↗
PubMed1985

Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow.

Haemopoietic radiation chimeras across the H-2 barrier (BALB/c----C57Bl/6; H-2d----H-2b chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57Bl/6 mice was injected i.p. into established chimeras (H-2d----H-2b). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c----C57Bl/6 or C57Bl/6----BALB/c chimeras. However, also inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c----C57Bl/6 chimeras, failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2d----H-2b chimeras displayed complete resistance to inculation of leukaemogenic H-2b restricted RadLV while all H-2b----H-2b, syngeneically reconstituted mice developed disseminated leukaemia. These findings demonstrate that: (a) a powerful suppressive principle operates in the chimeras which does not allow effector function and anti-tumour activity of passively transferred normal, mature T cells from resistant BALB/c mice. Thus, no H-2 restriction of donor T cells can be advocated for suppression of anti-tumour effector functions in the chimeras. (b) New donor (BALB/c, H-2d) marrow character in the H-2d----H-2b chimeras prevents expression of the H-2b restricted viral activity and leukaemogenic transformation and/or proliferation.

Animals↗
PubMed1984

Functional impairment of T-lymphocytes in mouse radiation chimeras by a nucleotide-free diet.

We examined the effect of a nucleotide-free diet on the immune function of mouse syngeneic bone marrow radiation chimeras. The graft-versus-host disease mortality assay revealed that GVH activity of spleen cells from radiation chimeras fed NFD (RCNFD) was reduced at 6-18 weeks after transplantation as compared with the radiation chimeras fed a control diet (RCCD). When tested 11-18 weeks after transplantation, the proliferative response of RCNFD spleen cells to phytohemagglutinin was significantly reduced at 11 and 13 weeks, the response to pokeweed mitogen (PWM) was significantly reduced at 11, 13, and 15 weeks, and the response to bacterial lipopolysaccharide remained virtually unaffected. At both six and eight weeks after transplantation, RCNFD and RCCD showed comparable numbers of CFUc/femur. RCNFD and RCCD did not differ significantly from each other in body weights or in spleen and bone marrow cellularity at 6-18 weeks after transplantation. These results suggest that dietary nucleotides are important for the normal function of mouse T-lymphocytes.

Animals↗
PubMed1989

Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer.

Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity. We concluded that enhanced nonspecific immune functions can in part compensate for the defective specific immune system after bone marrow transfer.

Animals↗
PubMedDate not supplied

[The bone marrow origin of the cells encapsulating a foreign body in the peritoneal cavity of xenogeneic radiation chimeras].

The origin and ultrastructure of the cells, encapsulating foreign body in peritoneal cavity of xenogeneic (rat in mouse) radiation chimeras was studied. The donor nature of the cells was identified by their karyotype and by DNA hybridization with rat ID-element. Cells with ultrastructural characteristics of fibroblasts encapsulating foreign body in the peritoneal cavity of the xenogeneic radiation chimeras were shown to originate from the transplanted (donor) bone marrow.

Animals↗
PubMed1992

Repopulation kinetics of intestinal intraepithelial lymphocytes in murine bone marrow radiation chimeras.

The kinetics of lymphoid cell repopulation of murine intestinal intraepithelial lymphocytes (IEL) from BM stem cells were studied in F1----parent radiation chimeras and were compared with T cell repopulation of the thymus and the spleen. T cells arising from donor bone marrow were present in the gut epithelium as early as day 5 postreconstitution in radiation chimeras. By day 7 postreconstitution, and at times thereafter, the IEL consisted of 70-95% CD3+ donor bone marrow-derived T cells, most of which were CD8+ cells with variable Thy-1 expression. CD4+8- IEL also were detected between days 7 and 14 postreconstitution; however, the CD4+8+ IEL subset did not appear within the gut epithelium until several weeks later and was followed by a progressive increase in the intensity of CD8 expression on CD4+8+ IEL. Functionally mature T cell receptor gamma/delta + and alpha/beta + IEL were present throughout repopulation of the gut epithelium. In contrast to the IEL, T cells were not detected in the thymus or the spleen until days 14 and 21 postreconstitution, respectively, and evidence of T cell function in the spleen was not detected until day 21 postreconstitution. These findings have implications for human bone marrow transplantation in that they demonstrate that T cell repopulation of the gut epithelium begins prior to T cell repopulation of the thymus and the spleen, and indicate that even in the presence of a thymus some IEL proceed through an extrathymic developmental pathway.

Animals↗
PubMed1989

Persistence of the irradiated host component in thymocyte populations from bone marrow radiation chimeras infected with lymphocytic choriomeningitis virus.

The thymus of chimeras made using T cell-depleted donor bone marrow from Thy1.1+ mice and 950 rad Thy 1.2+ recipients is dominated initially by cells expressing the Thy 1.2+ phenotype of the irradiated host. The thymocyte population recovered at 2 weeks after reconstitution comprises 80% Thy 1.2+ cells (host), the remainder being Thy 1.1+ (donor). This situation is normally reversed within a further week, with the host Ty 1.2+ (donor). This situation is normally reversed within a further week, with the host Thy 1.2+ thymocytes being present at a frequency of less than 5% from Week 4. Infection with lymphocytic choriomeningitis virus (LCMV) at 1 week after reconstitution with bone marrow causes a profound and persistent drop in the total number of thymocytes. The decline is equivalent for all categories of donor-derived thymocytes defined by two-color flow microfluorometric analysis for CD4 and CD8. However, there is a partial compensation by the retention of cells originating from the Thy 1.2+ host, which constitute 30-40% of the total thymocyte pool as late as 8 weeks after administration of bone marrow in the LCMV-infected chimeras. These radiation-resistant precursors give rise to CD4-8-, CD4-8+, CD4+8-, and CD4+8+ thymocytes, with the latter category being present at increased frequency. The potential skewing of the mature T cell repertoire as a consequence of persistent virus infection is discussed.

Animals↗
PubMed1972

Thymus-independent (B) cell proliferation in spleen cell cultures of mouse radiation chimeras stimulated by phytohemagglutinin or allogeneic cells.

Spleen cell cultures of radiation chimeras (thymectomized, lethally irradiated mice repopulated with bone marrow cells and thymocytes bearing different chromosomal markers) were stimulated by phytohemagglutinin (PHA) and F(1) allogeneic spleen cells. Karyotypic analyses showed a marked predominance of T mitoses on the 2nd and 3rd days of culture followed by a strong predominance of B mitoses on the 4th and 5th days. Analysis of cells undergoing their first mitoses showed that the majority of T mitoses on day 3 resulted from continuous T cell division, and that most cells entering their first mitoses at that time were of B type. Mixed lymphocyte cultures (MLC) of chimeras immunized against allogeneic spleen cells showed sometimes, but not always, a response different from "primary" MLC, with an earlier and stronger predominance of BM mitoses. The role of stimulated T cells in the induction of B mitoses was shown by (a) the incapacity of T-depleted spleen cells to be stimulated by PHA or in primary or secondary MLC, and (b) the restoration of the mitotic response of B cells to PHA by adding to the T cell-depleted culture either a very small number of T cell (identified by their different karyotype: "in vitro chimeras") or the cell-free supernatant of a 24 hr MLC.

Animals↗
PubMed1977

Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras.

The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production.

Animals↗