Abstract
We previously demonstrated selective enrichment of major histocompatibility complex (MHC) class II-specific autoreactive T cells in a subset of mouse CD4+ thymocytes. Here we show that a significant fraction of these autoreactive cells in the normal adult thymus expresses NK1.1 and high levels of Ly-6C and also exhibits flexibility in MHC restriction. In normal mice, this NK1.1+Ly-6Chi subfraction accounts for 10-50% of the CD4+ autoreactive subset and is enriched for MHC class II-restricted autoreactive cells as determined by mixed leukocyte reaction frequency analysis, similar to NK1.1-Ly-6C-CD4+ autoreactive cells. In contrast, in the thymus of class II-deficient littermate mice, NK1.1+Ly-6Chi cells account for most of the mature heat stable antigen (HSA)-CD4+ fraction and exhibit MHC-restricted non- class II autoreactivity. Thus, NK1.1+Ly-6ChiCD4+ T cells show flexibility in MHC class restriction, but their autoreactivity remains MHC dependent.
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Selected References
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- Arase H., Arase N., Ogasawara K., Good R. A., Onoé K. An NK1.1+ CD4+8- single-positive thymocyte subpopulation that expresses a highly skewed T-cell antigen receptor V beta family. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6506–6510. doi: 10.1073/pnas.89.14.6506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ballas Z. K., Rasmussen W. NK1.1+ thymocytes. Adult murine CD4-, CD8- thymocytes contain an NK1.1+, CD3+, CD5hi, CD44hi, TCR-V beta 8+ subset. J Immunol. 1990 Aug 15;145(4):1039–1045. [PubMed] [Google Scholar]
- Bendelac A., Killeen N., Littman D. R., Schwartz R. H. A subset of CD4+ thymocytes selected by MHC class I molecules. Science. 1994 Mar 25;263(5154):1774–1778. doi: 10.1126/science.7907820. [DOI] [PubMed] [Google Scholar]
- Bix M., Coles M., Raulet D. Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells. J Exp Med. 1993 Sep 1;178(3):901–908. doi: 10.1084/jem.178.3.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chambers W. H., Vujanovic N. L., DeLeo A. B., Olszowy M. W., Herberman R. B., Hiserodt J. C. Monoclonal antibody to a triggering structure expressed on rat natural killer cells and adherent lymphokine-activated killer cells. J Exp Med. 1989 Apr 1;169(4):1373–1389. doi: 10.1084/jem.169.4.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chan S. H., Cosgrove D., Waltzinger C., Benoist C., Mathis D. Another view of the selective model of thymocyte selection. Cell. 1993 Apr 23;73(2):225–236. doi: 10.1016/0092-8674(93)90225-f. [DOI] [PubMed] [Google Scholar]
- Cosgrove D., Gray D., Dierich A., Kaufman J., Lemeur M., Benoist C., Mathis D. Mice lacking MHC class II molecules. Cell. 1991 Sep 6;66(5):1051–1066. doi: 10.1016/0092-8674(91)90448-8. [DOI] [PubMed] [Google Scholar]
- Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
- Giorda R., Weisberg E. P., Ip T. K., Trucco M. Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1. J Immunol. 1992 Sep 15;149(6):1957–1963. [PubMed] [Google Scholar]
- Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
- Hayakawa K., Lin B. T., Hardy R. R. Murine thymic CD4+ T cell subsets: a subset (Thy0) that secretes diverse cytokines and overexpresses the V beta 8 T cell receptor gene family. J Exp Med. 1992 Jul 1;176(1):269–274. doi: 10.1084/jem.176.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jutila M. A., Kroese F. G., Jutila K. L., Stall A. M., Fiering S., Herzenberg L. A., Berg E. L., Butcher E. C. Ly-6C is a monocyte/macrophage and endothelial cell differentiation antigen regulated by interferon-gamma. Eur J Immunol. 1988 Nov;18(11):1819–1826. doi: 10.1002/eji.1830181125. [DOI] [PubMed] [Google Scholar]
- Kariv I., Hardy R. R., Hayakawa K. Selective enrichment of major histocompatibility complex class II-specific autoreactive T cells in the thymic Thy0 subset. J Exp Med. 1993 May 1;177(5):1429–1437. doi: 10.1084/jem.177.5.1429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levitsky H. I., Golumbek P. T., Pardoll D. M. The fate of CD4-8- T cell receptor-alpha beta+ thymocytes. J Immunol. 1991 Feb 15;146(4):1113–1117. [PubMed] [Google Scholar]
- MacDonald H. R., Howe R. C., Pedrazzini T., Lees R. K., Budd R. C., Schneider R., Liao N. S., Zinkernagel R. M., Louis J. A., Raulet D. H. T-cell lineages, repertoire selection and tolerance induction. Immunol Rev. 1988 Aug;104:157–182. doi: 10.1111/j.1600-065x.1988.tb00762.x. [DOI] [PubMed] [Google Scholar]
- Markowitz J. S., Rogers P. R., Grusby M. J., Parker D. C., Glimcher L. H. B lymphocyte development and activation independent of MHC class II expression. J Immunol. 1993 Feb 15;150(4):1223–1233. [PubMed] [Google Scholar]
- Takahama Y., Kosugi A., Singer A. Phenotype, ontogeny, and repertoire of CD4-CD8- T cell receptor alpha beta + thymocytes. Variable influence of self-antigens on T cell receptor V beta usage. J Immunol. 1991 Feb 15;146(4):1134–1141. [PubMed] [Google Scholar]
- Takahama Y., Sharrow S. O., Singer A. Expression of an unusual T cell receptor (TCR)-V beta repertoire by Ly-6C+ subpopulations of CD4+ and/or CD8+ thymocytes. Evidence for a developmental relationship between Ly-6C+ thymocytes and CD4-CD8-TCR-alpha beta+ thymocytes. J Immunol. 1991 Nov 1;147(9):2883–2891. [PubMed] [Google Scholar]
- Yoshimoto T., Paul W. E. CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994 Apr 1;179(4):1285–1295. doi: 10.1084/jem.179.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
