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B Is Required for the Positive Selection of CD8+ Thymocytes1
*
Laboratory of Cardiovascular Biology, Harvard School of Public Health, Boston, MA 02115; and
Harvard Medical School, Boston, MA 02115
To examine the role of NF-
B in T cell development, we analyzed
thymocyte ontogeny in transgenic (mutant I-B
(mI-B)) mice
that express a superinhibitory form of the NF-B inhibitory protein,
I-B (I-BA32/36), under the control of the T
cell-specific CD2 promoter and enhancer. Thymi from mI-B mice
contained increased numbers of double-positive (DP) and decreased
numbers of both CD4+ and CD8+ single-positive
cells, consistent with a block in DP thymocyte maturation. In addition,
expression of CD69, a marker of positive selection, was decreased on DP
thymocytes from the mI-B mice. To test directly whether NF-B
was required for positive or negative selection, we generated
mI-B mice expressing the H-Y or 2C ß TCR transgenes.
Expression of the I-BA32/36 transgene caused a block
in the positive selection of CD8+ single-positive cells in
both strains of TCR transgenic animals. In contrast, negative selection
was unaffected by expression of the I-BA32/36
transgene. Taken together, these results identified a NF-B-dependent
transcriptional pathway that is selectively required for the positive
selection of CD8+ thymocytes.
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