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NF-B Is Required for the Positive Selection of CD8⁺ Thymocytes¹

Thore Hettmann^* and Jeffrey M. Leiden^2,*,

^* 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-B_A32/36), 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-B_A32/36 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-B_A32/36 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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