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Human CD4 expression at the late single-positive stage of thymic development supports T cell maturation and peripheral export in CD4-deficient mice.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Oct 15; Vol. 169 (8), pp. 4347-53. - Publication Year :
- 2002
-
Abstract
- Positive selection of developing thymocytes is initiated at the double-positive (DP) CD4(+)CD8(+) stage of their maturation. Accordingly, expression of a human CD4 (hCD4) transgene beginning at the DP stage has been shown to restore normal T cell development and function in CD4-deficient mice. However, it is unclear whether later onset CD4 expression would still allow such a restoration. To investigate this issue, we used transgenic mice in which a hCD4 transgene is not expressed on DP, but only on single-positive cells. By crossing these animals with CD4-deficient mice, we show that late hCD4 expression supports the maturation of T cell precursors and the peripheral export of mature TCRalphabeta(+) CD8(-) T cells. These results were confirmed in two different MHC class II-restricted TCR transgenic mice. T cells arising by this process were functional in the periphery because they responded to agonist peptide in vivo. Interestingly, thymocytes of these mice appeared refractory to peptide-induced negative selection. Together, these results indicate that the effect of CD4 on positive selection of class II-restricted T cells extends surprisingly late into the maturation process by a previously unrecognized pathway of differentiation, which might contribute to the generation of autoreactive T cells.
- Subjects :
- Amino Acid Sequence
Animals
CD4 Antigens metabolism
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cell Differentiation genetics
Cell Differentiation immunology
Cell Movement genetics
Clonal Deletion genetics
Crosses, Genetic
Cytochrome c Group administration & dosage
Cytochrome c Group immunology
Gene Expression Regulation immunology
Histocompatibility Antigens Class II genetics
Humans
Injections, Intravenous
Lymphocyte Activation genetics
Mice
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
Organ Specificity genetics
Organ Specificity immunology
Peptides administration & dosage
Peptides immunology
Receptors, Antigen, T-Cell, alpha-beta biosynthesis
Stem Cells cytology
Stem Cells immunology
Stem Cells metabolism
T-Lymphocyte Subsets metabolism
Thymus Gland metabolism
Time Factors
CD4 Antigens biosynthesis
CD4 Antigens genetics
Cell Movement immunology
T-Lymphocyte Subsets cytology
T-Lymphocyte Subsets immunology
Thymus Gland cytology
Thymus Gland immunology
Transgenes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 169
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12370367
- Full Text :
- https://doi.org/10.4049/jimmunol.169.8.4347