Isolation and Identification of the Naturally Occurring, Newborn Spleen‐Associated Suppressor Cells

Peeler, K.; Wigzell, Hans; Peck, Ammon B.

doi:10.1111/j.1365-3083.1983.tb00811.x

Cited by 25 publications

(5 citation statements)

References 30 publications

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“…Protocols used in bone marrow reconstitutions of lethally yirradiated adult mice are detailed elsewhere (25). In brief, newborn spleen-associated null suppressor-inducer cells (26) were used to mediate bone marrow engraftment and to prevent graft versus host (GVH) disease. Newborn spleencell cultures were established by use of 6 x 10 6 spleen cells/ 35-cm 2 dish and 3 ml Eagle's high-amino acid (EHAA) medium supplemented with 0.5% normal mouse serum (27).…”

Section: Methodsmentioning

confidence: 99%

Reciprocal Allogeneic Bone Marrow Transplantation Between NOD Mice and Diabetes-Nonsusceptible Mice Associated With Transfer and Prevention of Autoimmune Diabetes

LaFace

Peck

1989

Diabetes

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Reciprocal allogeneic bone marrow transplantations were carried out between diabetes-susceptible nonobese diabetic (NOD) and diabetes-nonsusceptible C57BL/6 or B10.BR/cd mice to examine the role of the immune system and host environment in the development of autoimmune diabetes. Serotyping of lethally irradiated hosts reconstituted with allogeneic bone marrow showed the hematopoietically derived cells to be of donor origin. Our results showed that lethally irradiated NOD mice reconstituted with a B10.BR/cd hematopoietic cell system remained totally free of insulitis, failed to develop diabetes, and thrived to old age. In contrast, lethally irradiated C57BL/6 or B10.BR/cd mice reconstituted with an NOD hematopoietic cell system all developed insulitis, but only approximately 10% progressed to overt diabetes. Direct adoptive transfer of insulitis and diabetes by mature T-lymphocytes apparently was not required; analogous results were obtained when diabetes-nonsusceptible hosts were reconstituted with NOD hematopoietic cells containing T-lymphocytes or devoid of Thy-1+ cells. The difference in frequency for the development of insulitis versus insulitis plus overt diabetes in C57BL/6 and B10.BR/cd mice suggests that the hematopoietically derived immune cells from NOD mice were sufficient to induce anti-islet reactivity but may require the diabetogenic host environment to develop the frequency and severity of diabetes observed in NOD mice.

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Section: Methodsmentioning

confidence: 99%

Reciprocal Allogeneic Bone Marrow Transplantation Between NOD Mice and Diabetes-Nonsusceptible Mice Associated With Transfer and Prevention of Autoimmune Diabetes

LaFace

Peck

1989

Diabetes

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“…In this report we have investigated the ability of newborn spleen cells to modify and/or suppress lethal graft-versus-host reactivity and disease induced by adult cells injected into sublethally gamma-irradiated allogeneic or semi-allogeneic hosts. The rationale for this has been the ongoing studies by us [23,27] and others [1,8,17,24], indicating that newborn spleens contain a suppressor cell population that can suppress third-party adult allogeneic responses in vitro, combined with earlier work by Skowron-Cendrzak & Ptak [25,29], showing that newborn spleen cells can inhibit subsequent splenomegaly in donors engrafted with allogeneic adult cells. Results presented here indicate that third-party newborn spleen cells possess the potential to inhibit lethal graftversus-host disease in donor-recipient pairs mismatched at the entire H-2 complex (Tables II and III).…”

Section: Discussionmentioning

confidence: 99%

“…Preliminary data from several laboratories [3,4,23] suggest that newborn spleen cells elicit suppression in part through secretion of soluble factors. Argyris [3] has evidence of two factors, one with a molecular weight of less than 10,000, the second greater than 10,000.…”

Section: Discussionmentioning

confidence: 99%

“…Isolation of the effectors of this spleen-associated suppressor activity has revealed that these cells are not classical T lymphocytes but, instead, a mixed population of monocyte and mast cells [23,24]. This mixed population was shown by Peeler et al [23] to elicit its suppressor activity in part through secretion of soluble materials [3,4,23], which in turn apparently initiate activation ofthe suppressor limb of the immune response, including T suppressor cells. Similar suppressor activity is normally absent from the thymus cell population in the newborn [27], although VanBekkum& Knaan-Shanzer.…”

mentioning

confidence: 93%

“…Such naturally occurring suppressor cells can inhibit not only expression of alloreactivity in the newborn spleen per se [27] but also T-dependent and T-independent immune responses of third-party adult cells [3,4,8,16,17,25,27,29]. Isolation of the effectors of this spleen-associated suppressor activity has revealed that these cells are not classical T lymphocytes but, instead, a mixed population of monocyte and mast cells [23,24]. This mixed population was shown by Peeler et al [23] to elicit its suppressor activity in part through secretion of soluble materials [3,4,23], which in turn apparently initiate activation ofthe suppressor limb of the immune response, including T suppressor cells.…”

mentioning

confidence: 99%

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Naturally Occurring Spleen‐Associated Suppressor Activity of the Newborn Mouse

Jadus

Peck

1984

Scand J Immunol

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Spleens from newborn mice less than 6-7 days of age are known to contain naturally occurring suppressor cells, which can suppress the immune reactivity of third-party adult cells. In the present study newborn spleen cell populations are shown to possess the potential to inhibit lethal graft-versus-host (GVH) disease in sublethally gamma-irradiated hosts injected with allogeneic adult cells. However, this capacity to suppress GVH disease is controlled by at least two genetic restrictions: (1) the newborn spleen cells and the adult donor cells must be histocompatible at an H-2-linked region apparently telomeric of H-2DL, and (2) the newborn spleen cells must express a strongly stimulating non-H-2 (perhaps M1s) alloantigenic phenotype. Host animals that survive GVH remain chimeric for at least 3-4 weeks but return to the host phenotype by 8-10 weeks. Thus, it appears that in sublethally irradiated hosts the newborn cells suppress donor cell reactivity long enough for the host system to recover from the effects of irradiation.

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Characterization of the Natural Suppressor Cell Population in Adult Rat Bone Marrow

Noga

Wagner²,

Horwitz

et al. 1988

Journal of Leukocyte Biology

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Natural suppressor cell activity (NSCA) has been ascribed to a subset of cells present in human and murine hematopoietic tissues which can suppress a variety of lymphocyte responses without MHC restriction. We investigated NSCA in lymphocyte-depleted rat bone marrow (BM) which is used as a model for prevention of graft vs host disease (GVHD) following allogeneic BM transplantation (BMT). The T-cell depleted fraction obtained after elutriation contained higher levels of NSCA than the unseparated BM. Further separation of this graft fraction by discontinuous Percoll gradient centrifugation revealed high levels of radiosensitive NSCA in the low density (less than 1.070) fraction which represented 0.5% of the original BM population. These cells were of blast morphology, stained intensely with a dansylated derivative of cyclosporine A (dans CsA) and weakly expressed macrophage/granulocyte antigens and non-specific esterase (NSE). These cells were initially non-adherent but proliferated in culture to produce intensely NSE positive, adherent, phagocytic cells of macrophage morphology. We conclude that the highly suppressive, radiosensitive cell present in rat BM may be of early progenitor or monocyte lineage. The grafting of natural suppressor (NS) cells and progenitor cells may affect graft/host immunoregulation and their characterization may provide insight into GVH biology and graft rejection.

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Isolation and Identification of the Naturally Occurring, Newborn Spleen‐Associated Suppressor Cells

Cited by 25 publications

References 30 publications

Reciprocal Allogeneic Bone Marrow Transplantation Between NOD Mice and Diabetes-Nonsusceptible Mice Associated With Transfer and Prevention of Autoimmune Diabetes

Reciprocal Allogeneic Bone Marrow Transplantation Between NOD Mice and Diabetes-Nonsusceptible Mice Associated With Transfer and Prevention of Autoimmune Diabetes

Naturally Occurring Spleen‐Associated Suppressor Activity of the Newborn Mouse

Characterization of the Natural Suppressor Cell Population in Adult Rat Bone Marrow

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