MHC class II alleles associated with Th1 rather than Th17 type immunity drive the onset of early arthritis in a rat model of rheumatoid arthritis

Autor: Sabrina Haag, Jonatan Tuncel, Rikard Holmdahl
Rok vydání: 2016
Předmět:
0301 basic medicine
Arthritis
Autoimmunity
Immune responses
medicine.disease_cause
Lymphocyte Activation
T helper (Th) cells
Arthritis
Rheumatoid
chemistry.chemical_compound
0302 clinical medicine
Immunology and Allergy
Cytotoxic T cell
Research Articles
Interleukin-17
Cell Differentiation
3. Good health
Animal models
Immunodeficiencies and autoimmunity
Rheumatoid arthritis
Research Article|Basic
Immunology
chemical and pharmacologic phenomena
Biology
Major histocompatibility complex
03 medical and health sciences
Interferon-gamma
Immunity
medicine
Animals
Humans
Basic
Antibodies
Blocking
Alleles
MHC class II
Polymorphism
Genetic
Terpenes
Pristane
Histocompatibility Antigens Class II
Rats
Inbred Strains
Th1 Cells
medicine.disease
Arthritis
Experimental
Rats
030104 developmental biology
chemistry
biology.protein
Th17 Cells
MHC
030215 immunology
Zdroj: European Journal of Immunology
ISSN: 1521-4141
Popis: Polymorphisms in the MHC class II (MHCII) genes are strongly associated with rheumatoid arthritis, supporting the importance of autoreactive T helper (Th) cells for the development of this disease. Here, we used pristane‐induced arthritis (PIA), induced by the non‐antigenic hydrocarbon pristane, to study the impact of different MHCII alleles on T‐cell activation and differentiation. In MHCII‐congenic rats with disease‐promoting MHCII alleles, pristane primarily induced activation of Th1 cells, whereas activated T cells were Th17 biased in rats with protective MHCII alleles. Neutralization of IFN‐γ during T‐cell activation abrogated the development of disease, suggesting that Th1 immunity is important for disease induction. Neutralization of IL‐17, by contrast, suppressed arthritis only when performed in rats with established disease. Adoptive T‐cell transfers showed that T cells acquired arthritogenic capacity earlier in strains with a prevailing Th1 response. Moreover, upon pristane injection, these strains exhibited more Ag‐primed OX40+ and proliferating T cells of polyclonal origin. These data show that T cells are polarized upon the first encounter with peptide‐MHCII complexes in an allele‐dependent fashion. In PIA, the polyclonal expansion of autoreactive Th1 cells was necessary for the onset of arthritis, while IL‐17 mediated immunity contributed to the progression to chronic disease.
Using MHCII‐congenic rats injected with the hydrocarbon pristane, we show that Th‐differentiation is determined by the MHCII‐allele rather than by adjuvant‐induced cytokines. Strains with MHCII‐alleles that bias the immune response toward Th1 (FR61, DA) develop more severe arthritis with an earlier onset than strains with a Th17‐biased response (UR10, HR10).
Databáze: OpenAIRE
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