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M Bennett

Publications and source records attributed to M Bennett.

At least 451 records · Page 25Linked to original sources
PubMed1975

Loss of marrow allograft resistance in mice with transplanted methylcholanthrene-induced sarcomas.

To determine if the effector cells responsible for allogeneic marrow stem cell rejections were suppressed in mice with tumors, C57BL/6 (B6) mice were inoculated with 3-methylcholanthrene (MCA)-induced sarcoma cells. When the tumor reached 2.0--2.5 cm in diameter, these mice and control B6 and (BALB/c times A)F1 (CAF1) uninoculated animals were irradiated and given BALB/c marrow cells in the first of a two-step "stem cell rescue" experiment. Four days later, spleen cells of the primary hosts were reinoculated into irradiated CAF1 secondary hosts compatible with BALB/c marrow cells and immunized against B6 antigens. Splenic uptake (percent) of 125I-5-iodo-2'-deoxyuridine 5 days after spleen cell regrafting was used as a measure of cell proliferation and reflected growth of the stem cells in the primary hosts. BALB/c stem cells grew as well in B6 mice with tumors as in CAF1 primary hosts but were rejected by B6 controls. Seeding efficiency of BALB/c stem cells 6 hours after infusion of marrow cells and growth of syngeneic B6 stem cells were enhanced twofold in spleens of tumor-bearing B6 mice. To exclude the possibility that enhanced seeding resulted in greater survival of allogeneic stem cells, more DBA/2 marrow cells were infused into control B6 primary hosts than into tumor-bearing B6 and control DBA/2 mice. Control B6 mice resisted growth of even 7.5 times 10(6) DBA/2 marrow cells, whereas B6 tumor bearers allowed growth of 2.5 times 10(6) cells. No "suppressor cells" capable of inhibiting marrow cell allograft reactions were detected in spleens of tumor-bearing mice. Thus transplanted syngeneic MCA-induced sarcomas abrogated the ability of mice to reject allogeneic marrow stem cells.

Animals↗
PubMed1975

Casein-induced experimental amyloidosis. V. The response of lymphoid organs to T and B mitogens.

Functional and morphologic studies were performed on the lymphoid organs of inbred CBA/J mice receiving chronic casein administration. In the spleen, this regimen produces marked reticuloendothelial proliferation between 8 and 16 injections (preamyloid phase) and amyloid deposition between 16 and 24 injections. No amyloid was found in the thymus, lymph nodes, and bone marrow of these animals. Phytohemagglutinin and concanavalin A lymphocyte responses as measured by 3-H-thymidine incorporation were reduced in the spleen and lymph node of preamyloid animals but demonstrated partial recovery during the amyloid phase. Phytohemagglutinin and concanavalin A stimulation of thymic cells was significantly increased during both stages of amyloid induction, although the histologic studies revealed a marked involution of the thymic cortex. Lipopolysaccharide stimulation of spleen cells was normal in preamyloid and amyloid animals whereas in lymph node and bone marrow lipopolysaccharide responses were significantly decreased. The findings suggest a selective removal of subsets of T cell populations in the spleen and thymus and migration of B cells from bone marrow to the spleen during experimental amyloidosis.

Amyloidosis↗
PubMed1974

Mechanisms of genetic resistance to friend virus leukemia in mice.

Resistance to malignant erythropoiesis induced by Friend spleen focus-forming virus and resistance to marrow stem cell allografts are under genetic control. Strains of mice, e.g., C57BL/6 and B10.D2, which are homozygous for resistance at the Fv-2 locus, are also good rejectors of most bone marrow allografts. (89)Sr, a bone-seeking isotope, irradiates marrow but not other lymphoid organs and abrogates resistance to marrow allografts without suppressing T- or B-cell functions. Thus, marrow-dependent effector cells (M cells) seem to resist allogeneic stem cells. To test if the genetic resistance to Friend virus (FV) is also mediated by M cells, B6 mice were treated with (89)Sr using a dosage schedule known to abrogate resistance to allogeneic marrow cells. 9 days after FV infection of such mice, the spleens showed malignant erythroblastosis which could not be suppressed by prior hypertransfusion, a procedure which suppresses physiologic erythropoiesis. Such (89)Sr-treated B6 mice also supported extensive virus replication, while control mice did not. FV markedly suppressed the ability of (89)Sr-treated B6 mice to produce antisheep red blood cell (SRBC) antibodies, a feature seen normally only in genetically susceptible mice. Thus, (89)Sr-treated B6 mice behaved in these respects as if they were susceptible to FV. When increasing doses of (89)Sr were administered to B6 mice, a dose-related loss of resistance to FV was seen. Therefore, it appears that (89)Sr-sensitive M cells mediate the genetic resistance to FV. The results of experiments with (89)Sr indicated that genetically resistant mice would be expected to possess target cells which are susceptible to transformation by FV. To verify this corollary, bone marrow cells from B10.D2 (Fv-2(rr)) mice were transplanted into previously infected and lethally irradiated DBA/2 (Fv-2(ss)) recipients which share the same H-2(d) alleles. 5-15 days later, the spleens of DBA/2 primary recipients yielded transformed cells which were capable of producing splenic tumor colonies upon transplantation into adult, unirradiated B10.D2 secondary recipients. Various control experiments clearly indicated that the tumor colonies so induced were of B10.D2 marrow origin. This indicated that B10.D2 stem cells could be transformed when allowed to interact with FV in the spleens of susceptible DBA/2 mice. However, 30 days after transplantation of B10.D2 bone marrow cells into DBA/2 recipients, no transformed cells were detected. Apparently, in the 30-day interval precursors in the B10.D2 marrow gave rise to mature M cells which resisted the leukemic process. Since M cells recognize hybrid or hemopoietic histocompatability antigens expressed on primitive normal and transformed hematopoietic cells, we suggest that M cells may exert surveillance by rejecting leukemic cells. Thus, marrow transplantation from genetically resistant donors may provide a new mode of treatment for leukemia, by providing precursors of M cells and other immunocompetent cell types.

Animals↗
PubMed1973

Graft-versus-host reactions in mice. 3. Epithelioid and multinucleated giant cells of thymic origin.

Thymus cells from C3H donor mice were infused into lethally irradiated (C3H x C57BL/10)F(1) hybrid mice. Light and electron microscopic examination of the lymphoid tissues of recipients revealed the presence of epithelioid and multinucleated giant cells in addition to lymphocytes and histiocytes. Serial transplantation of thymus-derived cells into irradiated F(1) hybrid mice resulted in a preponderance of epithelioid cells over lymphocytes. Epithelioid cells, as well as lymphocytes and histiocytes, incorporated (3)H-thymidine, indicating that they were actively proliferating. Following transplantation of CBA-T6T6 thymocytes into irradiated (C3H x C57BL/10)F(1) mice, karyotypic analysis of host lymphoid tissues indicated that all dividing cells were of donor origin. Whereas bone marrow is known to give rise to epithelioid cells in the absence of thymic influences, the thymus must also contain precursors of epithelioid cells.

Animals↗
PubMed1973

Graft-versus-host reactions in mice. IV. Thymus cell suppression of antibody formation.

The ability of transplanted marrow-thymus cell mixtures to generate antibody-forming cells in irradiated syngeneic or F(1) hybrid mice when immunized with sheep erythrocytes 18 hours later was determined. Much fewer anti-sheep plaque-forming cells (PFC) were detected in spleens of F(1) hybrid mice. Adrenalectomy, use of infant recipient mice, or preimmunization of donors or hosts did not prevent the suppression; the grafting of irradiated donor-type spleen cells (source of "accessory" cells) produced only an additive effect. Parental marrow and thymus cells were able to generate new precursors of PFC and specific inducer cells, respectively, in spleens of F(1) hybrid mice, as detected by two-step experiments utilizing parent-strain secondary recipient mice. The suppression depended upon transferring parental strain thymus cells into F(1) hybrid mice and was seen irrespective of the marrow donor strain. When irradiated mice were immunized twice (on the day of transplantation and 4 days later), there was only marginal suppression of antibody production when marrow cells only or marrow plus thymus cells were transplanted. Thus, it appears that an excess of thymus-derived "suppressor" cells is generated upon exposure to alloantigens and inhibit terminal differentiation of antibody-forming cells in a noncytotoxic manner. Mature PFC themselves were not the targets of suppression. The method of immunization probably determines the relative functional capacity of thymus-derived "helper" and suppressor cells.

Adrenalectomy↗
PubMed1971

Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice.

F(1) hybrid mice are capable of rejecting inbred parental strain bone marrow grafts after a single lethal exposure to X-rays. The incompatibility is genetically controlled by the Hybrid-histocompatibility-1 (Hh-1) locus in or near the D end of the Histocompatibility-2 (H-2) region. The onset of parental graft rejection begins 9-12 hr after transplantation and is completed by 24 hr. Maturation of hybrid resistance does not occur until the 22nd day of life. In adults, the resistance to parental marrow grafts can be temporarily abrogated or weakened by administration of cyclophosphamide or dead cultures of Corynebacterium parvum, acute supralethal exposures to radiation, or by split-dose irradiation with 6-37-day intervals. Parental marrow grafts elicit a transplantation reaction in irradiated F(1) mice which is indistinguishable from that elicited in irradiated allogeneic (H-2-incompatible) hosts. Because of this immunogenetic similarity, the following question is raised: are the same or different alloantigens responsible for rejection of parental and allogeneic marrow grafts? In the first case, Hh-1 alleles would be recessive determinants of tissue-specific transplantation antigens, whereas in the second case they would be the determinants of parental- and tissue-specific antigens subject to genetic suppression in Hh-1 heterozygotes. Although the available evidence is not conclusive in excluding one of the two possibilities, it favors the concept that allograft reactivity to hemopoietic cells is elicited by recessive tissue-specific antigens.

Animals↗
PubMed1971

Sesame.

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Education of Persons with Intellectual Disabilitie↗
PubMed1971

Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated responder mice.

Mice are capable of rejecting H-2-incompatible bone marrow grafts after a single lethal exposure to X-rays. The onset of rejection begins 18-24 hr after transplantation and is completed by 96 hr. Maturation of this type of allograft reactivity does not occur until the 22nd day of life. In adult mice, the resistance to marrow allografts can be weakened by administration of cyclophosphamide or dead cultures of Corynebacterium parvum, but not heterologous anti-thymocyte serum. Sublethal exposures to X-rays 7 or 14 days before transplantation also weaken resistance. There is considerable interstrain variation in the ability of mice to resist allografts, even when H-2 differences between hosts and donor are kept identical. Although H-2 incompatibility is a necessary prerequisite for resistance, additional genetic factors influence the outcome of marrow allografts, presumably by controlling recognition. The regulator genes are determinant specific and the alleles for resistance or responder status appear to be dominant. The responder phenotype is expressed by hemopoietic cells and not by the environment. Accordingly, resistance is conferred to otherwise susceptible mice upon transfer of bone marrow cells but not of serum. The production and differentiation of effector cells for marrow graft rejection are thymus independent. In conclusion, bone marrow allografts elicit a particular transplantation reaction, previously unknown, in irradiated mice. Peculiar features of this reaction are the lack of proliferation of host lymphoid cells, tissue specificity, thymus independence, and regulation by genetic factors which apparently do not affect the fate of other grafts.

Animals↗