Contrasuppression. A novel immunoregulatory activity.

Gershon, Richard K.; Eardley, Diane D.; Durum, Scott K.; Green, Douglas R.; Shen, Francis X.; Yamauchi, Katsumi; Cantor, Harvey; Murphy, Donal B.

doi:10.1084/jem.153.6.1533

Cited by 188 publications

(60 citation statements)

References 18 publications

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“…This phenomenon was seen only in some genetic combinations, however, and not in the strain commonly used in EAE studies (Lewis). This could suggest an increased suppressor activity at the induc tion process of the disease as a result of the elimina tion of contrasuppressive cells [3] by splenectomy. Iv erson et al [4] studied immunoregulatory mechanisms at adoptive transfer of contact hypersensitivity and found an important role for contrasuppressive cells.…”

Section: Contrary To Mertin and Stackpoolementioning

confidence: 99%

Effect of Splenectomy on the Development of Experimental Autoimmune Encephalomyelitis in Rats with Different Genetic Background

Källén¹,

Nilsson²

1985

Int Arch Allergy Immunol

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We studied the effect of total or partial splenectomy on experimental autoimmune encephalomyelitis (EAE) development in rats with different genetic background after immunization with guinea pig basic encephalitogenic protein in Freund’s complete adjuvant. The operations did not affect some strains with a high susceptibility to EAE but may have reduced the EAE development in the Fischer strain, which shows only a weak susceptibility. In some hybrids and backcrosses, but not in others, splenectomy resulted in a clear-cut reduction of neurological signs of EAE. This effect may be ascribed to the elimination of contrasuppressive cell populations.

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Section: Contrary To Mertin and Stackpoolementioning

confidence: 99%

Effect of Splenectomy on the Development of Experimental Autoimmune Encephalomyelitis in Rats with Different Genetic Background

Källén¹,

Nilsson²

1985

Int Arch Allergy Immunol

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“…The word "contra-suppression" used here to describe the regulatory effects of PD-1 or Tim-3 on Treg cells remembers the old model of the suppression network dictating that immune homeostasis was guaranteed by a regulatory circuit including T-cell inducers of suppressor cells, suppressor T cells, and contra-suppressor T cells [21,22]. The studies on this fascinating theory were abandoned when modern molecular biology disavowed the existence of genes encoding antigen-specific soluble molecules derived from each single regulatory-cell population of the network [22].…”

mentioning

confidence: 99%

Induction, control, and plasticity of Treg cells: The immune regulatory network revised?

Barnaba

Schinzari

2013

Eur J Immunol

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The revival of the old and, for several years, abandoned era of suppressor T cells came in the 1990s with two works that resurrected the idea of CD8 + suppressor T cells [1,2]. The revival was further strengthened when a subset of CD4 + T cells constitutively expressing high levels of the IL-2R α-chain (CD25) and possessing suppressor activity was identified [3]. These cells, termed regulatory T (Treg) cells, were able to prevent disease in various models of autoimmunity, and to suppress transplant rejection and tumor immunity (as reviewed in [5,6]). The presence in the thymus of a subset of CD4 + CD25 + thymocytes that displayed suppressor activity indicated that Treg-cell development occurs in this organ (reviewed in [6]). However, the undisputed confirmation of the existence of Treg cells relates to the discovery that the genetic defect causing IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, also known as XLAAD (X-linked autoimmunity-allergic dysregulation syndrome)) in humans or Correspondence: Dr. Vincenzo Barnaba e-mail: vincenzo.barnaba@uniroma1.it the equivalent condition in mice (Scurfy mice) is due to mutations in the gene encoding the Foxp3 transcription factor, which is typically expressed in CD4 + CD25 high Treg cells (reviewed in [5,6]).The fundamental milestones that have supported the correlation between Foxp3 and the Treg-cell lineage are based on discoveries ascertaining that: (i) Foxp3 is absolutely required in Tregcell differentiation in the thymus, as indicated by the analysis of Foxp3-deficient mice and bone-marrow transfer studies; (ii) retroviral transfer of the Foxp3 gene into naïve T cells conferring suppressor activity and a Treg-cell phenotype; (iii) sustained Foxp3 expression in mature Treg cells being necessary to maintain the Treg-cell phenotype and function and preventing the cells trans-differentiating into different types of effector T cells; and (iv) the lack of Treg cells being the cause of fatal autoimmunity arising from Foxp3 deficiency in several experimental models (reviewed in [5,6]). In addition, the finding that some CD4 + T cells with either low CD25 levels or lacking CD25 (i.e., conventional T (Tconv) cells) can also express Foxp3 and display potent suppressor activity (reviewed in [6]) not only supported the key role of Foxp3 in Treg-cell differentiation but also suggested a dichotomy [7][8][9]. It has been proposed that demethylated TSDR is accessible to various transcription factors (CREB, activating transcription factor, etc.), and that it can hence act as an enhancer of the Foxp3 promoter, ultimately increasing the Foxp3 stabilization [7][8][9]. By contrast, TSDR is partially methylated in iTreg cells and this is associated with unstable Foxp3 expression and with the potentiality to convert into different effector T cell types, a process referred to as plasticity [7][8][9][10]. Indeed, under particular conditions in vitro (i.e., by using azacytidine inhibiting DNA methylation), iTreg cells can ultimately differentiate into fully ...

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“…Immunosuppression would teleologically suppress the inhibitor of the autoregulator, i.e. result in a net suppressive effect consistent with a network hypothesis (29)(30)(31).…”

Section: Discussionmentioning

confidence: 60%

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation.

et al. 1983

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A B S T R A C T In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (Ts/c) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/c ratios between 0.15 to 2.10, ratios of >0.8 correlated with AMLR responses (13/13), and ratios of <0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:Ts/c ratios or with the AMLR pre-or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The "naturally occurring" T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and Ts/c subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhib-

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Contrasuppression. A novel immunoregulatory activity.

Cited by 188 publications

References 18 publications

Effect of Splenectomy on the Development of Experimental Autoimmune Encephalomyelitis in Rats with Different Genetic Background

Effect of Splenectomy on the Development of Experimental Autoimmune Encephalomyelitis in Rats with Different Genetic Background

Induction, control, and plasticity of Treg cells: The immune regulatory network revised?

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation.

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