In vitro positive selection and anergy induction of class II-restricted TCR transgenic thymocytes by a cortical thymic epithelial cell line.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

In vitro positive selection and anergy induction of class II-restricted TCR transgenic thymocytes by a cortical thymic epithelial cell line.

Int Immunol. 1998 Sep;10(9):1335-46. Unique Identifier : AIDSLINE MED/99000399
Nelson AJ; Clegg CH; Farr AG; Department of Biological Structure, University of Washington,; Seattle, USA.

Abstract: Thymic epithelial cell lines isolated from hyperplastic thymi of transgenic mice over-expressing human papilloma viral oncogenes E6 and E7 constitutively displayed a phenotype consistent with a cortical origin. Exposure to IFN-gamma induced class II MHC and ICAM-1 expression, and up-regulated expression of VCAM-1 and class I MHC molecules. CD40 expression was maximally induced by a combination of IFN-gamma and IL-1, with lower levels of induction observed with a mixture of IFN-gamma and tumor necrosis factor (TNF)-alpha or TNF-alpha alone. B7-1 or B7-2 was not expressed constitutively or in response to cytokines. These stromal cells supported the development of CD4 single-positive (SP) cells in reaggregate co-cultures with CD4+ CD8+ thymocytes from TCR transgenic mice, but did not stimulate class II MHC-restricted, moth cytochrome c (MCC)-reactive T cells in vitro. The behavior of the culture system was consistent with positive selection, i.e. increased numbers of CD4 SP cells, gain of antigen responsiveness, and requirement for epithelial class II MHC products. Some variants of these stromal cell lines required exogenous MCC peptide in the reaggregation cultures (RC) for positive selection to occur. While a low concentration of MCC peptide (0.01-0.1 microM) significantly enhanced the accumulation of CD4 SP cells, higher concentrations of peptide (1-10 microM) resulted in recovery of predominantly CD4- CD8- and CD4(low) CD8- cells. Thymocytes recovered from RC containing low, but not high concentrations of peptide responded to MCC peptide in secondary cultures with splenic antigen-presenting cells.

Keywords: JOURNAL ARTICLE Animal Cell Line Clonal Anergy/*IMMUNOLOGY Cytochrome c/METABOLISM CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Epithelial Cells/CYTOLOGY Histocompatibility Antigens Class II/*IMMUNOLOGY Lymphocyte Transformation/IMMUNOLOGY Mice Mice, Transgenic Receptors, Antigen, T-Cell, alpha-beta/*GENETICS/*IMMUNOLOGY Stromal Cells/CYTOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Thymus Gland/*CYTOLOGY/*IMMUNOLOGY
990330
A9931114

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .