International Immunology, Vol 10, 1335-1346, Copyright © 1998 by Oxford University Press
AJ Nelson, CH Clegg and AG Farr
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.
ARTICLES
In vitro positive selection and anergy induction of class II-restricted TCR transgenic thymocytes by a cortical thymic epithelial cell line
Department of Biological Structure, University of Washington, Seattle, USA.
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