Factors influencing the human cytotoxic T cell response to autologous lymphoblastoid cell lines in vitro

Misko, Ihor S.; Soszynski, T. D.; Kane, R. G.; Pope, J. H.

doi:10.1016/0090-1229(84)90273-3

Cited by 18 publications

(7 citation statements)

References 36 publications

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“…In both cases it was more prominent when keratinocytes were stimulated with IFN gamma, inducing HLA class IT antigen expression and increasing the intensity of HLA class I expression. Similar results have also been reported in which CD4+ lymphocyte mediated cytotoxicity was found to be specific for components of FCS present in the culture medium and taken up by target cells (21). In our experiments, human serum was used in culture medium for HSV antigen priming of T lymphocytes and the keratinocytes were cultured in FCS.…”

Section: Resultssupporting

confidence: 68%

Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicity in vitro.

Cunningham¹,

Noble²

1989

J. Clin. Invest.

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In human recurrent herpetic lesions epidermal keratinocytes are induced to express HLA class II (DR) antigens. Keratinocytes derived from human split skin and cultured in vitro were induced to express HLA-DR but not -DQ antigens with IFN gamma preparations. These stimulated keratinocytes presented herpes simplex antigen directly to autologous blood-derived T lymphocytes in four of four subjects (stimulation indices: 1.5-2.7), suggesting that keratinocytes may have an accessory herpes simplex virus (HSV) antigen-presenting role in addition to the Langerhans cells and macrophages in herpetic skin lesions. Blood mononuclear cells from eight herpes simplex seropositive subjects which were activated in vitro by HSV antigen for 6 d showed cytotoxicity specific for HSV in infected autologous keratinocytes. This was significantly increased by prestimulation with IFN gamma (51-56% to 83-85%). In four of eight patients some cytotoxicity also occurred against uninfected, IFN gamma-stimulated keratinocytes. Lymphocyte subset analysis showed that cytotoxicity against HSV-infected, IFN gamma-stimulated keratinocyte targets was mediated by both CD3+ T lymphocytes and Leu llb+ natural killer cells. T lymphocyte cytotoxicity was mediated by both CD4+ and CD8+ T lymphocytes, suggesting a cytotoxic role for the activated CD4+ lymphocytes that initially predominate in herpetic lesions.

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Section: Resultssupporting

confidence: 68%

Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicity in vitro.

Cunningham¹,

Noble²

1989

J. Clin. Invest.

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“…la.b.c)., although scif-prelerred lysis was dominant throughout. Both the FCS-and HS-grown autologous LCL were lysed equally well by the EBV-specilk CTL in keeping wiih previous findings thai virus-specific lysis is independent of scrum effects [19]. Second, the haploidentieal LCL target cells (donors 4,5,8) bearing the HLA-AI, -B8, -DR3 paternal haplotype were not lysed by the specific CTL (Fig.…”

Section: Cytotoxieity Asiayssupporting

confidence: 55%

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen

Misko

Schmidt

Honeyman

et al. 1992

Clinical and Experimental Immunology

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SUMMARYThere are two lypes, A and B, of Epstein-Barr virus (EBV) and B95-8 represents the common lype A laboratory strain. Herein, we show in a family study thai paternal EBV-specific cyiotoxie T lymphocytes (CTL) generated in short-term cultures following stimulation with the autologous B95-8-lransformed lymphoblastoid cell line (LCL) or B cells freshly infected wilh the B95-8 isolate did not Iyse haptoidentiati B95-8 LCL expressing the HLA-AL -B8. -DR3 paternal haplotype. In contrast, the haploiUentical B95-8 LCL expressing the HLA-Al I, -B5i, -DR? paternal haplotype was sirongly lysed. Moreover, paternal CTL generated in response lo stimulation with the B95-8 LCL expressing the haploidentical HLA-Al. -B8, -DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV-specific response as shown by the poor lysis ofthe autologous LCL target cells. However, stimulation with the hapioidentieal HLA-Al I. -B51. -DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV-specific response. CTL clones were generated from two HLA-B8' donors in response to stimulation wilh the aulologous type A LCL transformed wiih wildlype EBV. The clones were cross-reactive for an immunodominant B95-8-associalcd peplide epitope ihat interacted with the HLA-B8 allcie but failed to Iyse B95-8-transfomied LCL largets unless the targets were prc-coated with ihe exogenous peptide. A CTL clone that was inilially stimulated wilh the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8 * donor, but failed to Iyse the B95-8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95-8 and the corresponding wildlype epitope. Our findings may help lo clarify the role of EBV in the pathogenesis of primary Sjogren's syndrome which is closely associated with HLA-B8.

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“…It has been suggested that stimulation of CTL in the presence of FBS can result in FBS-specific killing (32,33). When PBMC from EBV-seropositive donors were reactivated with LCL in presence of either 10% FBS or 10% HABS, there was little difference in the increase in expression of CD25, which peaked at ϳ9 -11 days (Table IV).…”

Section: Cd25-sorted Ctl Are Ebv Specific Even When Fbs Is Present Imentioning

confidence: 97%

Generation of EBV-Specific CD4+ Cytotoxic T Cells from Virus Naive Individuals

Savoldo

Cubbage

Durett

et al. 2002

The Journal of Immunology

104

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Adoptive immunotherapy with EBV-specific CTL (EBV-CTL) effectively prevents and treats EBV-driven lymphoproliferation in immunocompromised hosts. EBV-seronegative solid organ transplant recipients are at high risk of EBV-driven lymphoproliferation because they lack EBV-specific memory T cells. For the same reason, standard techniques for generating EBV-CTL in vitro from EBV-naive individuals are unsuccessful. To overcome this problem, we compared several methods of expanding EBV-CTL from seronegative adults and children. First, the standard protocol, using EBV-transformed lymphoblastoid B cell lines (LCL) as the source of APC, was compared with protocols using EBV-Ag-loaded dendritic cells as APC. Surprisingly, the standard protocol effectively generated CTL from all seronegative adults. The additional finding of EBV-DNA in the peripheral blood of three of these four adults suggested that some individuals may develop cellular, but not humoral, immune responses to EBV. By contrast, LCL failed to reactivate EBV-CTL from any of the six EBV-seronegative children. EBV-Ag-loaded dendritic cells could expand EBV-CTL, but only in a minority of children. However, the selective expansion of CD25-expressing T cells, 9–11 days after activation with LCL alone, proved to be a simple and reliable method for generating EBV-CTL from all seronegative children. The majority of these CTL were CD4+ (71 ± 26%) and demonstrated HLA class II-restricted, EBV-specific killing. Our results suggest that a negative EBV serology does not accurately identify EBV-negative individuals. In addition, our method for selecting EBV-specific CTL from naive individuals by precursor cell enrichment may be applicable to the immunotherapy of cancer patients with a low frequency of tumor- or virus-specific CTL.

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Factors influencing the human cytotoxic T cell response to autologous lymphoblastoid cell lines in vitro

Cited by 18 publications

References 36 publications

Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicity in vitro.

Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicity in vitro.

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen

Generation of EBV-Specific CD4+ Cytotoxic T Cells from Virus Naive Individuals

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