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Brief Definitive Report |
Correspondence to: J.W. Chamberlain, Research Institute, Programs in Infection, Immunity, Injury and Repair, and Genetics, The Hospital For Sick Children, Toronto, Ontario M5G 1X8, Canada. Tel:416-813-8323 Fax:416-813-8168 E-mail:jchamber{at}sickkids.on.ca.
Control of CD8
transcription during development of
/ß T cell receptor (TCR) T lymphocytes is mediated by at least two distinct stage-specific cis-acting transcriptional mechanisms (i.e., enhancers). On the CD8
-/-knockout (KO) background, cis-mechanism I and cis-mechanism II together mediate appropriate stage- and sublineage-specific transgenic (Tg) CD8
expression and "rescue" development of peripheral CD8+ single-positive (SP) cytotoxic T lymphocytes (CTLs). In contrast, on the wild-type (WT)/CD8+/+ or CD8
-/-KO backgrounds, a CD8
Tg directed by cis-mechanism I alone is activated during the double negative [DN] to double positive [DP] transition and expressed up to the CD3low/intermediate DP stage but not in more mature DP or SP thymocytes or peripheral T cells. As loss of cis mechanism I activity occurs around the onset of positive selection, it is possible that events associated with TCR/major histocompatibility complex (MHC) interactions and selection are involved in initiating these changes in CD8
transcription. To examine this issue, phenotypic and functional studies were performed for thymocytes and T cells of CD8
-/-KO mice that expressed a CD8
Tg under control of cis-mechanism I only. Despite loss of CD8
expression at the DP CD3low/intermediate stage, increased populations of mature CD3hiCD4-CD8- thymocytes and CD3+CD4-CD8- peripheral T cells were detected. By several criteria, including MHC class Irestricted antigen recognition, these cells have at least partially undergone positive and negative selection. Therefore, initiation of selection and sublineage commitment are determined before loss of cis-mechanism Imediated control of CD8
transcription. Further, CD8 expression beyond the CD3low/intermediate DP thymic stage is not essential for CTL development in vivo or function.
Key Words: CD8, gene expression, stage-specific regulation, thymic selection, sublineage commitment
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