Are MHC class II-restricted cytotoxic T lymphocytes important?

Braakman, Eric; Rotteveel, F. T. M.; Bleek, Grada van; Seventer, Gijs A. van; Lucas, C.J.

doi:10.1016/0167-5699(87)90185-x

Cited by 75 publications

(15 citation statements)

References 18 publications

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“…All nickel-specific Th2 clones were not cytolytic against keratinocytes, but efficiently killed B-LCL target cells through the Fas/FasL pathway. This may be an indication that the cytotoxicity of Th2 clones has an immunoregulatory function through the elimination of professional APC, as also proposed by others (56).…”

Section: Discussionmentioning

confidence: 71%

Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes

Traidl

Sebastiani

Albanesi

et al. 2000

The Journal of Immunology

138

115

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Allergic contact dermatitis (ACD) is the result of an exaggerated immune reaction to haptens mediated by skin-homing T cells, but the effector mechanisms responsible for the tissue damage are poorly understood. Here we studied the capacity of distinct subsets of hapten-specific T cells to induce apoptosis in autologous keratinocytes. Skin- and blood-derived nickel-specific CD8+ T cytotoxic 1 (Tc1) and Tc2 clones as well as CD4+ Th1 and Th2 expressed the cutaneous lymphocyte-associated Ag and exhibited strong MHC-restricted cytotoxicity against nickel-coupled B lymphoblasts, as detected by the [3H]TdR release assay. Both Tc1 and Tc2 clones, but not CD4+ T cells, displayed a significant cytotoxic activity against resting nickel-modified keratinocytes. Following IFN-γ treatment, keratinocytes expressed MHC class II and ICAM-1 and became susceptible to Th1-mediated, but not Th2-mediated, cytotoxicity. The molecules of the two major cytotoxic pathways, Fas ligand (FasL) and perforin, were expressed by Tc1, Tc2, and Th1 cells, whereas Th2 cells expressed only FasL. Experiments performed in the presence of specific inhibitors of the perforin (concanamycin A) and FasL (brefeldin A) pathway indicated that perforin-mediated killing dominated in Tc1 and Tc2, and FasL-mediated cytotoxicity prevailed in Th2 clones, with a more heterogeneous behavior in the case of Th1 cells. Finally, perforin mRNA was expressed in ACD lesional skin, as assessed by RT-PCR analysis. In aggregate, our results indicate that keratinocytes can be target of multiple hapten-specific CTL responses, that may have distinct roles in the epidermal injury during ACD.

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Section: Discussionmentioning

confidence: 71%

Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes

Traidl

Sebastiani

Albanesi

et al. 2000

The Journal of Immunology

138

115

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“…To exclude a possible inhibition of recognition of the antigen-MHC protein complex by the T-cell receptor, we tested tenascin effects in an antigen-specific, MHC class II-restricted target-cell killing model that is known to require the same a/f3 T-cell receptor involvement as in the proliferative response (37). The lack of inhibition (Fig.…”

mentioning

confidence: 99%

Tenascin, an extracellular matrix protein, exerts immunomodulatory activities.

Rüegg

Chiquet‐Ehrismann

Alkan

1989

Proc. Natl. Acad. Sci. U.S.A.

150

105

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Tenascin is a nonubiquitous extracellular matrix protein mainly expressed during morphogenesis in embryonal life. In adults it reappears in malignant tumors and during inflammation and tissue repair. Extracellular matrix proteins can alter cell morphology, adhesion, motility, differentiation, and growth. Since cells of the immune system can express receptors for extracellular matrix, we investigated the effects of tenascin on human monocytes and T and B lymphocytes. Tenascin inhibited monocyte adhesion to fibronectin and enhanced the LFA-1 (lymphocyte function-associated antigen l)-dependent clustering of Epstein-Barr virus-transformed B cells. The physiological consequences of the effects of tenascin were studied in several T-cell activation models. Tenascin inhibited T-cell activation induced by a soluble antigen (tetanus toxoid), alloantigens, or the mitogen concanavalin A. However, T-cell activation with phytohemagglutinin, crosslinked anti-CD3 antibody, or a mixture ofionomycin and phorbol ester was not inhibited by tenascin. Tenascin did not prevent interleukin 2-dependent T-cell growth or the cytolytic activity of an antigen-specific CD4+ T-cell clone. These results suggest that tenascin alters the adhesion properties of human monocytes, B cells, and T cells. The in vitro immunosuppressive activity of tenascin might be due to abrogation of an accessory cell function at an early stage of the interaction between antigenpresenting cells and T cells.

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“…Although CD4+ lymphocyte-mediated class IT-restricted cytotoxicity has also been well demonstrated in vitro against influenza and by clonal studies against HSV and measles (32-34), there is skepticism about the importance of their role in vivo (35). Further evidence for its importance in herpesvirus infections has been demonstrated recently with EBV and HSV infection (36,37).…”

Section: Resultsmentioning

confidence: 99%

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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Are MHC class II-restricted cytotoxic T lymphocytes important?

Cited by 75 publications

References 18 publications

Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes

Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes

Tenascin, an extracellular matrix protein, exerts immunomodulatory activities.

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.

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