Preferential Survival of CD8 T and NK Cells Expressing High Levels of CD94

Abstract
The Qa-1b/Qdm tetramer binds to CD94/NKG2 receptors expressed at high levels on ∼50% of murine NK cells. Although very few CD8 T cells from naive mice express CD94/NKG2 receptors, ∼50% of CD8 T cells taken from mice undergoing a secondary response against Listeria monocytogenes (LM) are CD94high and bind the tetramer. Although CD94int NK cells do not bind the tetramer, CD94int CD8 T cells do, and this binding is dependent on the CD8 coreceptor. We found that the extent of apoptosis in CD8 T and NK cells was inversely related to the expression of CD94, with lower levels of apoptosis seen in CD94high cells after 1–3 days of culture. The difference in CD8 T cell survival was evident as early as 6 h after culture and persisted until nearly all the CD94neg/int cells were apoptotic by 48 h. In contrast, expression of inhibitory Ly-49A,G2,C/I molecules was associated with higher levels of apoptosis. Cross-linking CD94/NKG2 receptors on CD8 T cells from a mouse undergoing an LM infection further reduced the percentage of apoptotic cells on the CD94-expressing populations, while cross-linking Ly-49I had no effect on CD8 T cells expressing Ly-49I. Cross-linking CD3 on CD8 T cells from a mouse undergoing a secondary LM infection increases the extent of apoptosis, but this is prevented by cross-linking CD94/NKG2 receptors at the same time. Similar results were observed with NK cells in that the CD94high population displayed less apoptosis than CD94int cells after 1–3 days in culture. Therefore, the expression of CD94/NKG2 is correlated with a lower level of apoptosis and may play an important role in the maintenance of CD8 T and NK cells.