Regulation of <i>in vitro</i> cytotoxic T lymphocyte generation. II. Demonstration of noncytotoxic alloantigen‐specific suppressor T lymphocytes

Schwartz, Anthony; Sutton, Sandra L.; Gershon, Richard K.

doi:10.1002/eji.1830120505

Cited by 20 publications

(4 citation statements)

References 36 publications

(7 reference statements)

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“…Although antigen-specific regulation of CTL induction by suppressor cells was described previously (1,20), regulation by soluble factors was not antigen specific (3,10,23). Thus the antigen-specific, genetically restricted suppressor factor regulating HSV-specific CTL induction that we observed represents a novel mechanism for CTL regulation.…”

Section: Discussionmentioning

confidence: 94%

Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice

Horohov¹,

Moore²,

Rouse³

1985

J Virol

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Indirect evidence indicates that herpes simplex virus (HSV)-specific cytotoxic-T-lymphocyte induction is regulated by suppressor cells. To search for such suppressor effects, supernatant fluids from splenocyte cultures from normal and HSV-immune mice cultured either with or without viral stimulation were tested for their ability to inhibit HSV-specific cytotoxic-T-lymphocyte induction. Only the supernatant fluid from the HSV-stimulated, HSV-immune cultures contained a suppressor activity (HSV-SF). HSV-SF was produced by nylon-wool-purified Thy 1+ cells. HSV-SF was detectable after 3 days of culture and would only suppress cytotoxic-T-lymphocyte induction if HSV-SF was added within 24 h of initiation of the test cultures. HSV-SF was neither dialyzable nor heat stable. Molecular sieve chromatography of HSV-SF yielded multiple peaks of suppressor activity. Although most of these peaks exhibited nonspecific suppressor activity, the suppression mediated by the 90,000 to 150,000-molecular-weight fractions was antigen specific and genetically restricted. These results provide direct evidence for the regulation of HSV-cytotoxic-T-lymphocyte induction by a novel suppressor factor.

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Section: Discussionmentioning

confidence: 94%

Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice

Horohov¹,

Moore²,

Rouse³

1985

J Virol

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“…Therefore, the gradually emerging concept of Tsr has been generally accepted. Suppressor T cells are heterogeneous; some of them work via cell‐to cell contact and others secrete inhibitory cytokines, such as interleukin (IL)‐10 or transforming growth factor‐beta (TGF‐β) 29,30 …”

Section: Hormonal Regulation Of Immunocompetencementioning

confidence: 99%

Neuroimmune Regulation in Immunocompetence, Acute Illness, and Healing

Berczi

Quintanar‐Stephano

Kovács

2009

Annals of the New York Academy of Sciences

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Adaptive immunocompetence is maintained by growth hormone (GH), prolactin (PRL), and vasopressin (VP). Innate or natural immunocompetence depends on cytokines, hormones (especially of the hypothalamus-pituitary-adrenal axis), and catecholamines. The acute phase response (APR, or acute febrile illness) is an emergency defense reaction whereby the adaptive, T cell-dependent, immune reactions are suppressed and the innate immune function is dramatically amplified. Infection and various forms of injury induce APR. Cytokines [interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-6] stimulate corticotropin-releasing hormone (CRH) and VP secretion and cause a "sympathetic outflow." Colony-stimulating factors activate leukocytes. CRH is a powerful activator of the pituitary adrenocortical axis and elevates glucocorticoid (GC) levels. Cytokines, GCs, and catecholamines play fundamental roles in the amplification of natural immune defense mechanisms. VP supports the APR at this stage. However, VP remains active and is elevated for a longer period than is CRH. VP, but not CRH, is elevated during chronic inflammatory diseases. VP controls adaptive immune function and stimulates adrenocorticotropic hormone (ACTH) and PRL secretion. PRL maintains the function of the thymus and of the T cell-dependent adaptive immune system. The ACTH-adrenal axis stimulates natural immunity and of suppressor/regulatory T cells, which suppress the adaptive immune system. VP also has a direct effect on lymphoid cells, the significance of which remains to be elucidated. It is suggested that VP regulates the process of recovery from acute illness.

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“…In addition, in vivo educated CTL present in the responder-cell population may suppress the MLR by lysing the stimulator cells [11,19]. On the other hand, lymphocytes alloactivated in the presence of ornithine [18], pyrilamine [16], cyclosporine [2,7], or stimulated with heat-inactivated allogeneic stimulator cells [10] are not cytotoxic, but do suppress, suggesting that other mechanisms than cytotoxicity might also be involved. Anti-idiotypic suppressive interactions [3], antigen-specific suppressor cells [5], or suppression by competition at the receptor level [1] have been suggested as possible mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic T Lymphocytes are the Prime Mediators of Suppression of the Mixed Lymphocyte Reaction by Alloactivated Cells

et al. 1989

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An alloactivated secondary mixed lymphocyte reaction (MLR) culture (SMC), which was suppressive in the MLR with autologous responder cells, was studied in more detail. In particular, we investigated whether the suppressive activity of this SMC was mediated by cytotoxic T cells or whether bona fide suppressor cells were involved. The SMC suppressed an MLR when the stimulator cells shared Bw57, Bw60, or Dw19 with the original stimulator. Separation of the SMC into CD4+ and CD8+ fractions demonstrated that the CD8+ fraction contained suppressive and cytotoxic activity against Bw57 or Bw60 antigens, while the CD4+ fraction contained both activities against the Dw19 specificity. The CD8+ fraction was also suppressive in the reverse MLR, while the CD4+ fraction was not. Limiting dilution analysis demonstrated that all CD8+-suppressive cultures were also cytotoxic, whereas in the CD4+ fraction both cytotoxic and non-cytotoxic suppressor cultures were found.

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Regulation of in vitro cytotoxic T lymphocyte generation. II. Demonstration of noncytotoxic alloantigen‐specific suppressor T lymphocytes

Cited by 20 publications

References 36 publications

Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice

Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice

Neuroimmune Regulation in Immunocompetence, Acute Illness, and Healing

Cytotoxic T Lymphocytes are the Prime Mediators of Suppression of the Mixed Lymphocyte Reaction by Alloactivated Cells

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