Tracing interactions of thymocytes with individual stromal cell partners
- PMID: 8625985
- DOI: 10.1002/eji.1830260426
Tracing interactions of thymocytes with individual stromal cell partners
Abstract
Cellular interactions in T cell development can be analyzed using thymus chimeras prepared in vitro, in which stromal cells and T cell precursors are manipulated separately. In an earlier study, we showed that for optimal T cell maturation most--if not all--stromal cells must display appropriate (selecting) major histocompatibility complex (MHC) molecules: the substitution of selecting by nonselecting stromal cells leads to a proportional decrease in mature T cell production. These data imply that the availability of selecting stromal micro-environments is rate limiting for positive selection, and that in positive selection each thymocyte engages only one (rather than multiple) stromal cell partners. To test this hypothesis, we developed a tracing system for thymocyte/stromal cell interactions, based on the acquisition by thymocytes of stroma-derived MHC class II determinants. When MHC class II-deficient precursors are placed in H-2b x k F1 environments (where all stromal cells co-express H-2b and H-2k), individual thymocytes acquire class II determinants of both haplotypes. In striking contrast, when placed in mosaic stromal environments (where stromal cells express either H-2b or H-2k evenly interspersed), individual thymocytes preferentially acquire MHC class II determinants of one or the other haplotypes, but rarely both. This provides strong evidence that thymocytes have intimate interactions with individual stromal cells: having engaged one stromal cell niche, thymocytes do not (or only rarely) have promiscuous liaisons with others.
Similar articles
-
Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment.J Immunol. 1999 Nov 1;163(9):4851-8. J Immunol. 1999. PMID: 10528186
-
Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex.Nature. 1996 Sep 5;383(6595):81-5. doi: 10.1038/383081a0. Nature. 1996. PMID: 8779719
-
Weak positive selection of transgenic T cell receptor-bearing thymocytes: importance of major histocompatibility complex class II, T cell receptor and CD4 surface molecule densities.Eur J Immunol. 1992 Mar;22(3):703-9. doi: 10.1002/eji.1830220313. Eur J Immunol. 1992. PMID: 1547816
-
Studying T-cell repertoire selection using fetal thymus organ culture.Methods Mol Biol. 2007;380:171-84. doi: 10.1007/978-1-59745-395-0_10. Methods Mol Biol. 2007. PMID: 17876093 Review.
-
Cellular interactions in thymocyte development.Annu Rev Immunol. 1996;14:73-99. doi: 10.1146/annurev.immunol.14.1.73. Annu Rev Immunol. 1996. PMID: 8717508 Review.
Cited by
-
Peptide-MHC heterodimers show that thymic positive selection requires a more restricted set of self-peptides than negative selection.J Exp Med. 2010 Jun 7;207(6):1223-34. doi: 10.1084/jem.20092170. Epub 2010 May 10. J Exp Med. 2010. PMID: 20457759 Free PMC article.
-
T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen-presenting cells.J Exp Med. 2000 Apr 3;191(7):1137-48. doi: 10.1084/jem.191.7.1137. J Exp Med. 2000. PMID: 10748232 Free PMC article.
-
The CD3-gammadeltaepsilon and CD3-zeta/eta modules are each essential for allelic exclusion at the T cell receptor beta locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-beta, -gamma, and -delta loci.J Exp Med. 1998 Jan 5;187(1):105-16. doi: 10.1084/jem.187.1.105. J Exp Med. 1998. PMID: 9419216 Free PMC article.
-
Molecular signature of recent thymic selection events on effector and regulatory CD4+ T lymphocytes.J Immunol. 2005 Nov 1;175(9):5751-8. doi: 10.4049/jimmunol.175.9.5751. J Immunol. 2005. PMID: 16237066 Free PMC article.
-
Functional development of the T cell receptor for antigen.Prog Mol Biol Transl Sci. 2010;92:65-100. doi: 10.1016/S1877-1173(10)92004-8. Prog Mol Biol Transl Sci. 2010. PMID: 20800817 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
