Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Desvignes, C; Etchart, N; Kehren, J; Akiba, I; Nicolas, JF; Kaiserlian, D.
Oral administration of hapten inhibits in vivo induction of specific cytotoxic CD8+ T cells mediating tissue inflammation: a role for regulatory CD4+ T cells.
J Immunol. 2000; 164(5):2515-2522
Doi: 10.4049/jimmunol.164.5.2515
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- Co-Autor*innen der Med Uni Graz
- Liechtenstein Nathalie
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- Abstract:
- We investigated whether oral tolerance could block the development of an inflammatory response mediated by CD8+ T cells, using a mouse model of oral tolerance of contact sensitivity (CS) to the hapten 2, 4-dinitrofluorobenzene (DNFB). In this system, the skin inflammatory response is initiated by hapten-specific class I-restricted cytotoxic CD8+ T (CTL) cells, independently of CD4 help. Oral delivery of DNFB before skin sensitization blocked the CS response by impairing the development of DNFB-specific CD8+ effector T cells in secondary lymphoid organs. This was shown by complete inhibition of DNFB-specific CTL and proliferative responses of CD8+ T cells, lack of specific IFN-gamma-producing CD8+ T cells, and inability of CD8+ T cells to transfer CS in RAG20/0 mice. RT-PCR and immunohistochemical analysis confirmed that recruitment of CD8+ effectors of CS in the skin at the site of hapten challenge was impaired in orally tolerized mice. Sequential anti-CD4 Ab treatment showed that only depletion of CD4+ T cells during the afferent phase of CS abrogated oral tolerance induction by restoring high numbers of specific CD8+ effectors in lymphoid organs, whereas CD4 depletion during the efferent phase of CS did not affect oral tolerance. These data demonstrate that a single intragastric administration of hapten can block in vivo induction of DNFB-specific CD8+ CTL responsible for tissue inflammation and that a subset of regulatory CD4+ T cells mediate oral tolerance by inhibiting expansion of specific CD8+ effectors in lymph nodes.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Oral -
- Adoptive Transfer -
- Animals -
- CD4-Positive T-Lymphocytes - immunology
- DNA-Binding Proteins - genetics DNA-Binding Proteins - immunology
- Dermatitis, Contact - genetics Dermatitis, Contact - immunology Dermatitis, Contact - pathology
- Dinitrofluorobenzene - administration and dosage Dinitrofluorobenzene - immunology
- Epitopes, T-Lymphocyte - immunology
- Female -
- Haptens - administration and dosage Haptens - immunology
- Immune Tolerance - genetics Immune Tolerance - immunology
- Interferon-gamma - biosynthesis
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- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Oxazolone - administration and dosage Oxazolone - immunology
- Skin - immunology Skin - metabolism
- T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism T-Lymphocytes, Cytotoxic - transplantation
- Transposases - genetics Transposases - immunology