Expression of Inhibitory Receptors Ly49E and CD94/NKG2 on Fetal Thymic and Adult Epidermal TCR V_#gamma#3 Lymphocytes

摘要

Ly49 and CD94/NKG2 inhibitory receptors are predominantly expressed on murine NK cells, but they are also expressed on a subvpopulation of peripheral CD8 memory TCR #alpha##beta# lymphocytes. In this study we demonstrate that Ly49E and CD94/NKG2 receptors are expressed on mature TCR V_#gamma#3~+ cells in the fetal thymus. Expression correlated with a memory phenotype, such as expression of CD44, 2B4, and IL-2R#beta# (CD122), and absence of IL-2R#alpha# (CD25) expression. No expression of Ly49A, C, D, G2, or I receptors was observed. This phenotype is similar to that of fetal thymic NK cells. SKin-located V_#gamma#3 T cells, the progeny of fetal thymic V_#gamma#3 cells, also expressed CD94/NKG2 and Ly49E but not the other members of the Ly49 family. The development and survival of Ly49E~+ or CD94/NKG2~+ V_#gamma#3 T lymphocytes was not dependent upon expression of MHC class I molecules. The cytotoxicity of TCR V_#gamma#3 cells was inhibited when Qdm, the ligand for CD94/NKG2, was presented by Ql1~b-transfected target cells. Also, upon cross-linking of CD94/NKG2 with mAb 3S9, TCR V_#gamma#3 thymocytes were prevented from killing Fc_#gamma#R~+ P815 target cells. These effects were most pronounced in the CD94/NKG2~high subpopulation as compared with the CD94/NKG2~low subpopulation of V_#gamma#3 cells. Our data demonstrate that V_#gamma#3 T cells expressing inhibitory Ly49E and CD94/NKG2 receptors are mature and display a memory phenotype, and that CD94/NKG2 functions as an inhibitory receptor on these T lymphocytes.