Protection of Lethally Irradiated Mice by Spleen Cells from Neonatally Thymectomized Mice

Yunis, E. J.; Good, Robert A.; Smith, Julius; Stutman, Osias

doi:10.1073/pnas.71.6.2544

Cited by 29 publications

(9 citation statements)

References 12 publications

(10 reference statements)

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“…Although we have not, in these experiments, verified the presence of MTV in the C3H, A.CA and RIII strains, these are known to be infected by this (Vlahakis, 1973) or immunosuppressive effects of their respective MTVs (Stutman, personal communication) or from differences in sensitivity to the induction of immunological tolerance in general, as suggested by some results (Yunis et al, 1974). A strong effect of hormonal status might also explain the different rates of appearance of mammary tumours in C3H and A.CA mice.…”

Section: Discussionmentioning

confidence: 60%

Influence of milk source on transplantability of histocompatible mammary tumours in mice

Oth¹,

Sabolović²

1977

Br J Cancer

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It is confirmed that C3H mammary tumours are much more easily transplantable in histocompatible recipients when these have been reared on C3H milk, than when they have been reared on milk from the inbred Swiss/B strain. By contrast, A.CA mammary tumours transplanted in histocompatible hosts reared on A.CA or Swiss/B milk, grow almost equally well in both sorts of recipient. Thus, rearing on Swiss/B milk has different effects on the transplantability of mammary tumours of C3H and A.CA. On the other hand, recipients which were reared on C3H or A.CA milks accept grafts of C3H mammary tumours about equally, suggesting that milks from A.CA and C3H have the same effect on the transplantability of C3H mammary tumours. The different action of Swiss/B milk on tumours of C3H and A.CA seems best attributed to differences between C3H and A.CA tumours or between mouse strain genotypes. By contrast, the transplantability of C3H mammary tumours is significantly changed when the recipients were reared on milk from the RIII strain instead of C3H. These facts suggest that the milk from RIII has an action which differs from that of both C3H and A.CA in this respect. The data are discussed on the basis of a differential tollerance-inducing action of mammary tumour viruses (MTVs) which infect C3H, A.CA and RIII, and have an important role in tumour induction.

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Section: Discussionmentioning

confidence: 60%

Influence of milk source on transplantability of histocompatible mammary tumours in mice

Oth¹,

Sabolović²

1977

Br J Cancer

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“…Several explanations can be offered: (i) a larger number of lymphocytes may be needed to elicit a GVH reaction than to produce a skin allograft rejection. (ii) Irradiation injury of the thymic stroma may be dose-dependent and have a threshold that was exceeded in some of our experiments with 884 rads (3,23). This dose of radiation may have injured the thymic stroma, interfering with maturation of a T-cell subpopulation that is ultimately involved in inducing GVH reactions.…”

Section: Discussionmentioning

confidence: 99%

“…However, as expected, neonatal allogeneic thymocytes (30)(31)(32), and also allogeneic spleen cells from either 6-day-old or adult donors, did not protect the mice lethally irradiated (884 rads). On the other hand, mice sublethally irradiated (512 rads) do not survive after engrafting with allogeneic newborn thymus cells or adult spleen cells.-Failure to protect lethally irradiated mice and death of sublethally irradiated mice treated with allogeneic cells can almost certainly be attributed to their capacity to initiate the GVH reaction (23,33,34) (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

“…Further, radiation chimeras often have long-persisting, subnormal immune responses and lymphoid atrophy and are susceptible to infection (17)(18)(19)(20)(21). It has been suggested that this deficiency may in some way be caused by irradiation, e.g., through injury to the thymus (3,22,23), or by damage to a host cell that exerts an important helper function in T cell immunities.…”

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confidence: 99%

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Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution.

Tulunay¹,

Good²,

Yunis³

1975

Proc. Natl. Acad. Sci. U.S.A.

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After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection. These observations contribute to understanding of some of the persisting immunodeficiencies that are observed in man after fatal irradiation and bone marrow transplantation. These results should suggest better approaches to more effective cellular engineering for correction of immunodeficiency diseases and for treatment of immunodeficiency diseases and of leukemias and malignancies of man.

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“…Results of transplants for these and other congenital disorders have recently been reviewed [17], Unfortunately, normal HLA-identical sibling donors are available for only about 40% of cases. While conven tional marrow grafts from related or even unrelated donors, mismatched for HLA-A or HLA-A and HLA-B haplotype, have led to immunologic reconstitution in several patients, these grafts have often been complicated by severe acute and chronic GVHD and, in some cases, Early attempts to transplant HLA-haplotype-disparate bone marrow into patients with SCID consistently either failed to engraft, or produced fatal GVHD [4,21], How ever, the few successful fully allogeneic fetal liver trans plants in patients with SCID [22][23][24] underscored what had already been well documented in animal models of marrow transplantation: that hematopoietic cells de pleted of mature T lymphocytes could reconstitute immune function in MHC-haplotype or fully mismatched recipients without risk of severe or fatal GVHD [25][26][27][28][29], In 1980, we described a technique for removing T lymphocytes from human bone marrow for transplanta tion [30], This technique, modified to facilitate treatment of large marrow volumes [31], involves selective removal of mature blood elements with soybean agglutinin (SB A); residual T lymphocytes are subsequently removed from the unagglutinated marrow fraction by differential sedi mentation of cells that form rosettes with sheep red blood 1 Supported by US PHA grants Ca-33050, Ca-08748, The Vincent Astor Foundation, and The Robert J. Kleberg and Helen C. Kleberg Foundation.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of HLA-Haplotype Disparate Parental Marrow Grafts Depleted of T Lymphocytes by Differential Agglutination with a Soybean Lectin and E-Rosette Depletion for the Treatment of Severe Combined Immunodeficiency

Reisner¹,

O'Reilly²,

Brochstein³

et al. 1986

Vox Sanguinis

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The factors that impact upon successful bone marrow transplantation leading to immunologic reconstitution in severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome, and in other lethal congenital immunodeficiencies are reviewed. Evidence is presented that graft-versus-host disease (GVHD) can be abrogated by the depletion of T cells, even from histoincompatible marrow grafts. However, graft resistance or restricted immune reconstitution has been observed with significant frequency. The bases for T cell reconstitution and limitations in B cell humoral immune recovery in the postgrafting period are reviewed, together with emerging evidence that pretransplant cytoreduction might obviate some of these problems.

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Protection of Lethally Irradiated Mice by Spleen Cells from Neonatally Thymectomized Mice

Abstract: Long-lived, immunologically vigorous (C3Hf X Af)Fl hybrids were produced after lethal irradia-

Cited by 29 publications

References 12 publications

Influence of milk source on transplantability of histocompatible mammary tumours in mice

Influence of milk source on transplantability of histocompatible mammary tumours in mice

Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution.

Evaluation of HLA-Haplotype Disparate Parental Marrow Grafts Depleted of T Lymphocytes by Differential Agglutination with a Soybean Lectin and E-Rosette Depletion for the Treatment of Severe Combined Immunodeficiency

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