Abstract
To investigate the contribution of human leukocyte antigen (HLA) class II molecules in susceptibility to inflammatory demyelination, we induced experimental autoimmune encephalomyelitis (EAE) in transgenic (tg) mice expressing the HLA-DR3, HLA-DQ8 and HLA-DQ6 molecules in the absence of endogenous class II (Ab°). Following immunization with mouse myelin, HLA-DR3 tg mice mounted strong T-cell proliferative responses, and developed inflammatory lesions and demyelination in the central nervous system with mild to moderate clinical symptoms of EAE. HLA-DQ8 and HLA-DQ6 tg mice elicited weak T-cell proliferative responses and did not develop clinical symptoms of EAE. HLA-DR3/DQ6 double tg mice immunized with mouse myelin experienced clinical disease similar to the single tg HLA-DR3 tg mice, indicating that expression of DQ6 in this line had no effect on disease. In contrast, HLA-DR3/DQ8 double tg mice developed severe inflammatory lesions and clinical disease in response to immunization with mouse myelin. Our data suggest that in the presence of two susceptible class II alleles, namely HLA- DR3 and DQ8, there is additional selection and expansion of potential autoreactive T cells, resulting in enhanced severity of disease. (C) American Society for Histocompatibility and Immunogenetics, 2000.
| Original language | English |
|---|---|
| Pages (from-to) | 279-289 |
| Number of pages | 11 |
| Journal | Human Immunology |
| Volume | 61 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2000 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Immunology
- Immunology and Allergy
Cite this
Complementation between specific HLA-DR and HLA-DQ genes in transgenic mice determines susceptibility to experimental autoimmune encephalomyelitis. / Das, Pritam; Drescher, Kristen M.; Geluk, Annemieke; Bradley, David S.; Rodriguez, Moses; David, Chella S.
In: Human Immunology, Vol. 61, No. 3, 03.2000, p. 279-289.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Complementation between specific HLA-DR and HLA-DQ genes in transgenic mice determines susceptibility to experimental autoimmune encephalomyelitis
AU - Das, Pritam
AU - Drescher, Kristen M.
AU - Geluk, Annemieke
AU - Bradley, David S.
AU - Rodriguez, Moses
AU - David, Chella S.
PY - 2000/3
Y1 - 2000/3
N2 - To investigate the contribution of human leukocyte antigen (HLA) class II molecules in susceptibility to inflammatory demyelination, we induced experimental autoimmune encephalomyelitis (EAE) in transgenic (tg) mice expressing the HLA-DR3, HLA-DQ8 and HLA-DQ6 molecules in the absence of endogenous class II (Ab°). Following immunization with mouse myelin, HLA-DR3 tg mice mounted strong T-cell proliferative responses, and developed inflammatory lesions and demyelination in the central nervous system with mild to moderate clinical symptoms of EAE. HLA-DQ8 and HLA-DQ6 tg mice elicited weak T-cell proliferative responses and did not develop clinical symptoms of EAE. HLA-DR3/DQ6 double tg mice immunized with mouse myelin experienced clinical disease similar to the single tg HLA-DR3 tg mice, indicating that expression of DQ6 in this line had no effect on disease. In contrast, HLA-DR3/DQ8 double tg mice developed severe inflammatory lesions and clinical disease in response to immunization with mouse myelin. Our data suggest that in the presence of two susceptible class II alleles, namely HLA- DR3 and DQ8, there is additional selection and expansion of potential autoreactive T cells, resulting in enhanced severity of disease. (C) American Society for Histocompatibility and Immunogenetics, 2000.
AB - To investigate the contribution of human leukocyte antigen (HLA) class II molecules in susceptibility to inflammatory demyelination, we induced experimental autoimmune encephalomyelitis (EAE) in transgenic (tg) mice expressing the HLA-DR3, HLA-DQ8 and HLA-DQ6 molecules in the absence of endogenous class II (Ab°). Following immunization with mouse myelin, HLA-DR3 tg mice mounted strong T-cell proliferative responses, and developed inflammatory lesions and demyelination in the central nervous system with mild to moderate clinical symptoms of EAE. HLA-DQ8 and HLA-DQ6 tg mice elicited weak T-cell proliferative responses and did not develop clinical symptoms of EAE. HLA-DR3/DQ6 double tg mice immunized with mouse myelin experienced clinical disease similar to the single tg HLA-DR3 tg mice, indicating that expression of DQ6 in this line had no effect on disease. In contrast, HLA-DR3/DQ8 double tg mice developed severe inflammatory lesions and clinical disease in response to immunization with mouse myelin. Our data suggest that in the presence of two susceptible class II alleles, namely HLA- DR3 and DQ8, there is additional selection and expansion of potential autoreactive T cells, resulting in enhanced severity of disease. (C) American Society for Histocompatibility and Immunogenetics, 2000.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033994751&partnerID=8YFLogxK
U2 - 10.1016/S0198-8859(99)00135-4
DO - 10.1016/S0198-8859(99)00135-4
M3 - Article
C2 - 10689117
AN - SCOPUS:0033994751
VL - 61
SP - 279
EP - 289
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 3
ER -