T-cell-mediated cytotoxicity against herpes simplex virus-infected target cells

Pfizenmaier, Klaus; Starzinski‐Powitz, Anna; Röllinghoff, Martin; Falke, D.; Wagner, Hermann

doi:10.1038/265630a0

Cited by 78 publications

(39 citation statements)

References 9 publications

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“…Early studies had shown that while CTL from lymph nodes draining sites of HSV-1 infection failed to lyse infected targets directly ex vivo, these same cells could be converted to good effectors by culturing them for 3 days in vitro in the absence of exogenous antigen (30,31). We had previously shown that HSV-1 gB-specific CD8 ϩ T cells could be detected within the activated subset of popliteal lymph nodes draining infected tissues with the V␤10 marker in combination with TCR ␤-chain sequences, which are both signatures for this specificity (8).…”

Section: Resultsmentioning

confidence: 99%

Herpes Simplex Virus Type 1-Specific Cytotoxic T-Lymphocyte Arming Occurs within Lymph Nodes Draining the Site of Cutaneous Infection

Cose

Coles

Winterhalter

et al. 2000

J Virol

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Various studies have shown that major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL) can be isolated from lymph nodes draining sites of cutaneous infection with herpes simplex virus type 1 (HSV-1). Invariably, detection of this cytolytic activity appeared to require some level of in vitro culture of the isolated lymph node cells, usually for 3 days, in the absence of exogenous viral antigen. This in vitro "resting" period was thought to represent the phase during which committed CD8 ؉ T cells become "armed" killers after leaving the lymph nodes and prior to their entry into infected tissue as effector CTL. In this study we reexamined the issue of CTL appearance in the HSV-1 immune response and found that cytolytic activity can be isolated directly from draining lymph nodes, although at levels considerably below those found after in vitro culture. By using T-cell receptor elements that represent effective markers for class I-restricted T cells specific for an immunodominant glycoprotein B (gB) determinant from HSV-1, we show that the increase in cytotoxicity apparent after in vitro culture closely mirrors the expansion of gB-specific CTL during the same period. Taken together, our results suggest that HSV-1-specific CTL priming does not appear to require any level of cytolytic machinery arming outside the lymph node compartment despite the absence of any detectable infection within that site.Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) can play a critical role in antiviral immune responses (40). These T cells facilitate viral clearance by directly lysing target cells harboring productive virus infection. In the case of the human immune response to herpes simplex virus type 1 (HSV-1), CD8 ϩ T cells can be isolated from infected individuals (32). In addition, the recent identification of the HSV-encoded ICP47 protein, which blocks class I-restricted peptide presentation, suggests that CTL lysis plays an important role during the antiviral response (11,15,39). In mouse model systems, CD8 ϩ T cells can be isolated from lymph nodes draining the site of cutaneous primary infection, and these T cells effectively protect animals against subsequent infection (2, 3, 13, 22, 28). However, unlike many primary antiviral responses, T cells isolated from lymph nodes draining sites of cutaneous HSV-1 infection did not appear to kill infected target cells without being subjected to a period of in vitro culture, usually in the absence of exogenous antigen (6,27,30). This culture period was thought to reflect a need for extralymphoid differentiation into armed cytotoxic effectors capable of dealing with the peripheral infection. Such a proposal is consistent with the notion that while CTL precursors are activated within the draining lymph nodes, the cytotoxic effectors are required only within the actual sites harboring infective virus, in this case the infected footpads.We have examined the CD8 ϩ CTL response to footpad infection with HSV-1. This response is d...

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Section: Resultsmentioning

confidence: 99%

Herpes Simplex Virus Type 1-Specific Cytotoxic T-Lymphocyte Arming Occurs within Lymph Nodes Draining the Site of Cutaneous Infection

Cose

Coles

Winterhalter

et al. 2000

J Virol

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“…The SV model has some properties in common with other virus models while it differs in other respects. Priming with inactivated virus and secondary challenge with inactivated virus has been possible with SV [2, 13, 27, 281, rabies virus [29] and influenza viruses [30,31], but not with vaccinia [32,33] and herpes virus ( [34], M. Rollinghoff, personal communication). Paramyxoviruses are known for their fusion capacity while other viruses are less effective in this respect.…”

Section: Discussionmentioning

confidence: 99%

Generation of virus‐specific cytotoxic T cells in vitro I. Induction conditions of primary and secondary Sendai virus‐specific cytotoxic T cells

Koszinowski

Simon

1979

Eur J Immunol

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Heidelberg H-Zrestricted cytotoxic T cells specific for Sendai virus were generated in vitro in a primary response from normal mouse lymphocytes cultured in the presence of infective as well as inactivated Sendai virus. Antigen-presenting cells of different origin, including T cells, were found to be effective stimulators. Antibodies to Sendai virus were shown to inhibit the activation of specific precursor killer cells when added to cultures before, but not after, the addition of viral antigen. Data obtained by Lyt phenotyping, revealed that precursor killer cells specific for Sendai virus reside in the Lyt-2,3+ T cell population and that Lyt-1,2,3+ T cells are not required for the generation of cytotoxic lymphocytes. Different activation kinetics were demonstrated for primary and secondary antiviral cytotoxic responses, and the analysis of the proliferation and stimulation requirements suggests qualitative differences.

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“…Immune lymph node cells for the acute CTL populations were obtained by draining the popliteal and retropharyngeal lymph nodes of mice inoculated 5 days previously in the rear footpads and ear flaps with l06 TCIDso of HSV-1 KOS. Cells were then cultured in vitro in the absence of exogenous antigen for 3 days as described previously (Pfizenmaier, 1977). On the final day of culture, CTL activity was determined using sodium [51Cr]chromate-labelled (200 pCi) mock-or virus-infected target cells in a 4 h assay, as previously described (Lawman et al, 1980).…”

Section: Delayed Type Hypersensitivity (D Th)mentioning

confidence: 99%

Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0

Martin

Zhu

Silverstein

et al. 1990

Journal of General Virology

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Vaccinia virus recombinants expressing the herpes simplex virus type 1 (HSV-1) genes encoding ICP0 or ICP4 were used to identify the precise target antigen(s) of murine anti-viral cytotoxic T lymphocytes (CTL) specific for the non-structural immediate early proteins. These studies revealed that HSV-l-specific CTL, restricted to class I major histocompatibility complex genes of the H-2 k haplotype but not the H-2 d or H-2 b haplotypes, would lyse autologous cells expressing ICP4. HSV-l-specific CTL derived from various mice strains failed to lyse target cells expressing ICP0. Calculation of the frequencies of H-2k-restricted virusspecific CTL demonstrated that approximately a third of the total HSV-l-specific response was directed against ICP4. Immunization of mice with either recombinant vaccinia virus or transfected L cells expressing ICP4 induced HSV-l-specific lymphoproliferation and delayed hypersensitivity but CTLs were not induced. More importantly, such immunized animals were unable to resist or control a subsequent challenge with virulent HSV-1.

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T-cell-mediated cytotoxicity against herpes simplex virus-infected target cells

Cited by 78 publications

References 9 publications

Herpes Simplex Virus Type 1-Specific Cytotoxic T-Lymphocyte Arming Occurs within Lymph Nodes Draining the Site of Cutaneous Infection

Herpes Simplex Virus Type 1-Specific Cytotoxic T-Lymphocyte Arming Occurs within Lymph Nodes Draining the Site of Cutaneous Infection

Generation of virus‐specific cytotoxic T cells in vitro I. Induction conditions of primary and secondary Sendai virus‐specific cytotoxic T cells

Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0

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