Evidence for Two Types of Non‐specific Suppressor Cells Activated by the Graft‐versus‐Host Reaction in Mice

Parthenais, Elaine; Lapp, Wayne S.

doi:10.1111/j.1365-3083.1978.tb00446.x

Cited by 19 publications

(9 citation statements)

References 21 publications

(9 reference statements)

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“…These observations raised the possibility that the early macrophage-mediated suppression represented an amplified normal immune regulatory function (Elie & Lapp 1977) and could serve as a model for the phenomenon of antigenic competition (Lawrence & Simonsen 1967, Moller 1971, Sjoberg 1971, 1972. At the time when the macrophage population had reached maximum numbers there was a functional shift in the population from cells that displayed accessory cell function to those that manifested a purely suppressor cell function without a concomitant accessory cell function (Elie & Lapp 1977, Parthenais et al 1974, Parthenais & Lapp 1978. More recent studies have shown that macrophage suppression may be mediated by a marked increase in prostaglandin E (PGE) release from splenic, lymph node and thymic macrophages which peaked on d 9 post-GvH induction.…”

Section: Early Suppressive Events -Evidence For Suppressor Cellsmentioning

confidence: 99%

The Functional and Histological Basis for Graft‐versus‐Host‐Induced Immunosuppression

Lapp

Ghayur

Mendes

et al. 1985

Immunological Reviews

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The GvH reaction resulting from the injection of parental strain cells into adult F1 hybrids suppresses both cell-mediated and humoral immune responses and is dependent on the donor-host combination and the number of parental cells used to induce the GvH reaction. The early suppression is due, at least in part, to the increased number of macrophages and the activation of suppressor macrophages which act directly on the T-helper cell and perhaps the B-cell as well. The macrophage suppression is associated with an increase in PGE production. The long-term T-cell immunodeficiency is mediated by GvH-induced thymic dysplasia resulting in a block or an arrest in T-cell differentiation and deficient IL-2 production. The B-cell immunodeficiency is associated with both a decrease in B-cell production from lymphoid progenitors and a decrease in CFU-s production. The GvH reaction induces 2 types of thymic lesion, a stress-related effect causing atrophy of the thymic cortex and a cytolytic process causing severe-to-moderate lesions in the thymic medulla as a consequence of injury to medullary epithelial cells and a loss of Hassall's corpuscles (thymic dysplasia). By employing the NK-cell-deficient beige mutation, it was shown that the severe-to-moderate thymic medullary lesions occurred in F1 mice only in those transplant situations in which the donor inoculum was of the +/bg genotype, regardless of the genotype of the recipient. It is proposed that activation of parental T cells may contribute to the early immunosuppressive events; however, the relatively permanent immunosuppression appears to be associated with NK-like effector cells which are capable of causing injury to lymphoid and epithelial tissue, especially epithelium of the thymic medulla. These studies raise the possibility that the GvH reaction may contribute to some T- and B-cell immunodeficiencies observed in the SCID and AIDS syndromes, as well as in patients following bone marrow transplantation.

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Section: Early Suppressive Events -Evidence For Suppressor Cellsmentioning

confidence: 99%

The Functional and Histological Basis for Graft‐versus‐Host‐Induced Immunosuppression

Lapp

Ghayur

Mendes

et al. 1985

Immunological Reviews

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“…A GVHR induced in animals, may result in a state of immune deficiency (for a reveiw, see Grebe & Streilein 1976). The mechanisms behind this immunodeficiency are not fully understood, but it has been claimed that macrophages may serve as suppressor cells and that the function of helper T-and B-cells is also impaired (Sjoberg 1972, Elie & Lapp 1976, Elie & Lapp 1977, Treiber & Lapp 1978, Parthenais & Lapp 1978. This agrees with observations of BMT in humans with GVHD, who are especially prone to die of fatal infections (Neiman et al 1977, Winston et al 1979.…”

Section: Gvhd and Immunodeficiencymentioning

confidence: 99%

Are Increased IgE‐Levels a Signal of an Acute Graft‐Versus‐Host Reaction?

Ringdén¹,

Persson²,

Johansson³

1983

Immunological Reviews

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IgE-levels are markedly elevated following bone-marrow transplantation in patients with and without GVHD. In patients with GVHD, there is a significant correlation between the timing of the IgE-increase and the appearance of clinical GVHD (p less than 0.01). The highest IgE-level (8000 kU/l) was noted in a recipient of a syngeneic graft. During the IgE-peak, the serum from this patient contained low concentrations of IgE reacting with several tested allergens as well as for the hapten TNP, which indicated polyclonal activation. In a patient with a known allergy to animal danders, RAST tests were positive against dog and cat both before and six weeks after total body irradiation and transplantation with marrow from a non-allergic donor. A slight increase in the amount of allergen-specific, IgE-antibodies was seen during the increase in total IgE. A non-allergic patient was transplanted with marrow from a donor allergic to timothy. Timothy-specific, IgE-antibodies were detected immediately after transplantation but they disappeared within a few days and could not be detected during the period of increase in total IgE. We believe that the IgE-elevation seen after conditioning with cytotoxic drugs and total body irradiation in BMT-patients is a polyclonal response in host B-cells induced during an acute, GVHR and influenced by disturbed regulatory T-cells. Lymphocytes from patients with acute GVHD had unusually large numbers of IgG/PFC in vitro after stimulation with staph. aureus Cowan 1 (p less than 0.001), which may reflect a clonal expansion of responsive B-cells.

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“…Mice were immunized intravenously with 5 x 10 s SRBC in 0.3 ml saline. 4 d later the direct splenic PFC response was assessed by the method of Cunningham and Szenberg (29) as modified in this laboratory (30).…”

Section: Methodsmentioning

confidence: 99%

Thymic selection and thymic major histocompatibility complex class II expression are abnormal in mice undergoing graft-versus-host reactions.

Desbarats

Lapp

1993

The Journal of Experimental Medicine

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Sumnlal~The graft-vs.-host reaction (GVHR) results in damage to the epithelial and lymphoid compartments of the thymus and thus in abnormal maturation and function of thymocytes in mice undergoing GVHR. In this report, the effects of GVHR on thymic T cell receptor (TCR) expression and usage have been investigated. GVHK was induced in unirradiated F1 hybrid mice by the intravenous transfer of parental lymphoid cells. Expression of the CD3/TCR complex on thymocyte subsets defined by CD4 and CD8 was studied by three-color flow cytometry. The level of CD3/TCK was decreased on CD4+CD8 -, but not CD4-CD8 § mature thymocytes. The lack of upregulation of CD3/TCR on CD4 single-positive thymocytes, but not on their CD8 + counterparts, suggested an abnormality of class II major histocompatibility complex (MHC) expression in the thymuses of mice undergoing GVHK. Immunofluorescence staining of thymic frozen sections revealed that MHC class II expression was dramatically decreased in GVH-reactive mice. GVHK-induced changes in positive and negative selection were evaluated by determining the incidence of specific VB TCK segment usage in the thymus. In normal mice, thymocyte usage of any given V3 segment was highly consistent between individuals of the same strain and age; however, a marked divergence in the incidence of TCK V36 hi and VB8 hi cells between GVH-reactive littermate mice was observed, suggesting that thymic positive selection had become disregulated in these animals. Furthermore, negative selection was defective; the incidence of phenotypically self-reactive VB6 hi T cells was significantly greater in the thymuses of GVHreactive mice bearing the endogenous superantigen Mls-P than in untreated controls. Thus, mice undergoing GVHK showed defective TCK upregulation on CD4+CD8 -thymocytes and changes in TCK usage reflecting aberrant thymic selection, in conjunction with decreased expression of MHC class II. Most abnormalities of TCR expression and usage on CD4 + thymocytes observed in GVH-reactive mice were analogous to those of class II knockout mice.

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Evidence for Two Types of Non‐specific Suppressor Cells Activated by the Graft‐versus‐Host Reaction in Mice

Cited by 19 publications

References 21 publications

The Functional and Histological Basis for Graft‐versus‐Host‐Induced Immunosuppression

The Functional and Histological Basis for Graft‐versus‐Host‐Induced Immunosuppression

Are Increased IgE‐Levels a Signal of an Acute Graft‐Versus‐Host Reaction?

Thymic selection and thymic major histocompatibility complex class II expression are abnormal in mice undergoing graft-versus-host reactions.

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