Tolerance and suppression of immunity to herpes simplex virus: different presentations of antigens induce different types of suppressor cells

Schrier, Rachel; Pizer, Lewis I.; Moorhead, John W.

doi:10.1128/iai.40.2.514-522.1983

Cited by 22 publications

(15 citation statements)

References 23 publications

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“…In that study, they demonstrated that suppression of the HSV-DTH response by T suppressor cells inhibited the immunopathological damage. Many others have also demonstrated that the HSV-specific DTH reaction is subject to modulation by suppressor cells at either the afferent or efferent level (21,29). In our CD8+-depleted mice, we could still demonstrate potent DTH reactions although, perhaps unexpectedly, these were not increased in magnitude over those observed in nonsuppressed mice.…”

Section: Discussionsupporting

confidence: 42%

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology

Newell

Martin

Sendele

et al. 1989

J Virol

119

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Herpetic stromal keratitis (SK), a frequent cause of visual impairment, is considered to represent an immune-mediated inflammatory response to persistent herpes simplex virus virions or subcomponents within the corneal stroma. The experimental disease in mice involves the essential participation of T lymphocytes, but the role of T-lymphocyte subsets in either mediating or controlling the disease is uncertain. In this report, rat monoclonal antibodies were used to selectively deplete mice in vivo of CD4+ (helper-inducer) and CD8+ (cytotoxic-suppressor) T-cell populations and the effect on herpetic SK was evaluated. As measured by flow cytometry, mice treated with anti-CD4 monoclonal antibody (GK 1.5) were >95% depleted of CD4+ T lymphocytes and mice treated with anti-CD8 monoclonal antibody (2.43) were 90% depleted of CD8+ T lymphocytes. Depleted and nonspecific mouse ascites-treated control mice were infected topically on the corneas with herpes simplex virus type 1, and the induction of various immune parameters during the acute infection was evaluated. CD4+-depleted mice failed to produce either a significant antiviral antibody or delayed-type hypersensitivity response but were capable of producing normal cytotoxic T-lymphocyte responses. In contrast, CD8+-depleted mice produced antiviral antibody and delayed-type hypersensitivity responses comparable with those in control animals, but cytotoxic T-lymphocyte responses were markedly reduced. Clinical observations of the corneas revealed that SK in CD4+-depleted mice was significantly reduced, whereas in CD8+-depleted mice SK developed more rapidly, was more severe, and involved a greater percentage of mice. These observations implicate the CD4+ T-lymphocyte subset as the principal mediators of SK and CD8+ T lymphocytes as possible regulators that control the severity of SK.

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Section: Discussionsupporting

confidence: 42%

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology

Newell

Martin

Sendele

et al. 1989

J Virol

119

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“…T,-aff block the early afferent phase of the DH response involving the induction and clonal expansion of DH-mediating T cells. T,-eff, on the other hand, act later in the efferent phase by blocking the expression of primed DH-mediating T cells (13). Both T, are virus-specific in their action; i.e., T, raised in mice with HSV-induced tolerance did not affect the DH response to a different virus, vesicular stomatitis virus.…”

mentioning

confidence: 97%

“…In most of these studies the coupled antigen has been a simple hapten. Recently, we have described the induction of tolerance mediated by Ts by using lymphoid cells coupled with a complex antigen, namely herpes simplex virus (HSV) (13). Spleen cells (SC) infected with HSV when injected intravenously (i.v.)…”

mentioning

confidence: 99%

“…Spleen cells (SC) infected with HSV when injected intravenously (i.v.) into mice were shown to induce tolerance in mice to an HSVspecific DH response (13).…”

mentioning

confidence: 99%

“…of soluble virus results in the induction of afferent-acting T, (Ts-aff), whereas i.v. injection of HSV-infected syngeneic SC induces T,-aff as well as efferent-acting Ts (Ts-eff) (13). Both types of T, suppress the DH response to HSV, but they act on different limbs of the response.…”

mentioning

confidence: 99%

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Different forms of membrane-associated herpes simplex virus glycoproteins induce functionally distinct subsets of herpes simplex virus-specific suppressor T cells

Ishioka¹,

Pizer²,

Moorhead³

1985

J Virol

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Previous studies have shown that two types of virus-specific suppressor T cells (Ti) are induced in mice made tolerant with herpes simplex virus (HSV)-infected spleen cells (SC). One type of T. blocks the afferent phase of the delayed hypersensitivity response to HSV (T.-aff), and the other blocks the efferent or effector phase (Ts-eff). In this report we show that the induction requirements for these suppressor populations differ. Injection of SC infected for 6 h with HSV at a multiplicity of infection of 5 or less or treated with heat-inactivated virus induced only Ts-aff. Similar results were seen with SC incubated for 90 min in virus-free preparations containing only viral proteins. In contrast, the Ts-eff population was induced only by SC treated for 6 h with infectious HSV at a multiplicity of infection of 10. Collectively, these data indicate that Ts-aff are induced by adsorbed HSV antigens on SC, whereas Ts-eff are induced by nascent HSV antigens expressed on infected SC. In addition to their induction requirements, the two types of regulatory cells differ in their expression of effector function. Ts-eff but not Ts-aff require a cyclophosphamide-sensitive target cell in the immune recipient for suppressor function. The possible identity of this target cell and the significance of the different induction requirements between the two types of Ts are discussed.

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Split tolerance of T_hl and T_h2 cells in tolerance to Theiler's murine encephalomyelitis virus

et al. 1993

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Theiler's murine encephalomyelitis virus (TMEV) produces a chronic, inflammatory demyelinating disease in susceptible mouse strains that is used as a model for multiple sclerosis. Because disease susceptibility correlates temporally with the development of virus-specific delayed-type hypersensitivity (DTH) responses, we studied methods and mechanisms by which virus-specific DTH could be specifically inhibited. The intravenous injection of UV-inactivated TMEV coupled to syngeneic splenocytes via a carbodiimide linkage (TMEV-SP), prior to immunization, induced a significant degree of tolerance in virus-specific helper (Th) cells as determined by decreased DTH and T cell proliferative responses, and decreased interleukin (IL)-2 and interferon (IFN)-gamma protein and mRNA levels. In contrast to the reduced levels of Th1-specific lymphokine mRNA levels, IL-4-specific mRNA levels in response to virus stimulation were not affected in tolerant mice. Surprisingly, the total anti-TMEV antibody response in DTH tolerant mice was enhanced 20-100-fold over sham-tolerized controls and was composed of reduced levels of anti-virus IgG2a, but dramatically increased levels of anti-virus IgG1. The "split-tolerance" was antigen specific, dependent on the concentrations of TMEV and carbodiimide used in the coupling procedure, and varied with the number of coupled syngeneic splenocytes administered. The fixative effects of carbodiimide on antigen-presenting function were necessary for the induction of DTH tolerance with TMEV-SP, since intravenous administration of virus coupled to splenocytes via a biotin-avidin linkage led to enhanced virus-specific antibody responses, but was unable to inhibit DTH unless concomitantly fixed with carbodiimide. Collectively, the data indicate that Th1 cells (mediating DTH, IL-2 and IFN-gamma production, and helper function for IgG2a production) were specifically anergized, with concomitant stimulation of Th2 cells (producing IL-4 and mediating helper function for IgG1 antibody production).

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Tolerance and suppression of immunity to herpes simplex virus: different presentations of antigens induce different types of suppressor cells

Cited by 22 publications

References 23 publications

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology

Different forms of membrane-associated herpes simplex virus glycoproteins induce functionally distinct subsets of herpes simplex virus-specific suppressor T cells

Split tolerance of T_hl and T_h2 cells in tolerance to Theiler's murine encephalomyelitis virus

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Tolerance and suppression of immunity to herpes simplex virus: different presentations of antigens induce different types of suppressor cells

Cited by 22 publications

References 23 publications

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology

Different forms of membrane-associated herpes simplex virus glycoproteins induce functionally distinct subsets of herpes simplex virus-specific suppressor T cells

Split tolerance of Thl and Th2 cells in tolerance to Theiler's murine encephalomyelitis virus

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Split tolerance of T_hl and T_h2 cells in tolerance to Theiler's murine encephalomyelitis virus