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A multiple transgenic mouse model with a partially humanized activation pathway for helper T cell responses.
- Source :
-
Journal of immunological methods [J Immunol Methods] 2000 Dec 01; Vol. 246 (1-2), pp. 37-50. - Publication Year :
- 2000
-
Abstract
- Mice expressing human CD4 and human MHC II molecules provide a valuable model both for the investigation of the immunopathogenetic role of human autoantigens and for the development of therapeutic strategies based on modulating helper T cell activation in vivo. Here we present a novel mouse model expressing HLA-DR17 (a split antigen of HLA-DR3) together with human CD4 in the absence of murine cd4 (CD4/DR3 mice). Human CD4 accurately replaces murine cd4 within T cells. In particular, the preservation of cd8(+) and CD4(+) T cell subsets distinguishes CD4/DR3 mice from other multiple transgenic models in which the alternative T cell subsets are fundamentally disturbed. Moreover, human CD4 is also faithfully expressed on antigen presenting cells such as dendritic cells and monocyte/macrophages, so that the overall transgenic CD4 expression pattern resembles very closely that of humans. HLA-DR3 expression in the thymus correlates very closely to that of mouse MHC II. In contrast, only 70% of mouse MHC II positive cells in spleen, lymph node, and peripheral blood coexpress HLA-DR3. No significant bias was found with regard to particular leucocytes in this respect. The stimulation of helper T cells clearly depends on the interaction between the human transgene products, since mAbs to HLA-DR and/or CD4 completely blocked in vitro recall responses to tetanus toxoid. CD4/DR3 mice represent a partially humanized animal model which will facilitate studies of DR3-associated autoimmune responses and the in vivo determination of the therapeutic potential of mAbs to human CD4.
- Subjects :
- Animals
Antibodies, Monoclonal immunology
Antibodies, Monoclonal pharmacology
Antigen-Presenting Cells immunology
Antigen-Presenting Cells metabolism
CD4 Antigens biosynthesis
CD8 Antigens immunology
Crosses, Genetic
Down-Regulation
Female
Gene Expression
HLA-DR3 Antigen biosynthesis
Humans
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Lymphatic System immunology
Lymphatic System metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Models, Animal
Phenotype
T-Lymphocyte Subsets immunology
T-Lymphocytes, Helper-Inducer metabolism
Tetanus Toxoid immunology
Transgenes
CD4 Antigens genetics
CD4 Antigens immunology
HLA-DR3 Antigen genetics
HLA-DR3 Antigen immunology
Lymphocyte Activation immunology
T-Lymphocytes, Helper-Inducer immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1759
- Volume :
- 246
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Journal of immunological methods
- Publication Type :
- Academic Journal
- Accession number :
- 11121545
- Full Text :
- https://doi.org/10.1016/s0022-1759(00)00288-x