Modulation of T-cell functions in KIR2DL3 (CD158b) transgenic mice

In humans, a minor subset of T cells express killer cell Ig-like receptors (KIRs) at their surface. In vitro data obtained with KIR+ alpha beta and ga mma delta T-cell clones showed that engagement of KIR molecules can extingu ish T-cell activation signals induced via the CDB/T-cell receptor (TCR) com plex. We analyzed the T-cell compartment in mice transgenic for KIR2DL3 (Tg -KIR2DL3), an inhibitory receptor for HLA-Cw3. As expected, mixed lymphocyt e reaction and anti-CD3 monoclonal antibody (MoAb)-redirected cytotoxicity exerted by freshly isolated splenocytes can be inhibited by engagement of t ransgenic KIR2DL3 molecules. In contrast, antigen and anti-CD3 MoAb-induced cytotoxicity exerted by alloreactive cytotoxic T lymphocytes cannot be inh ibited by KIR2DL3 engagement, In double transgenic mice, Tg-KIR2DL3 x Tg-HL A-Cw3, no alteration of thymic differentiation could be documented. Immuniz ation of double transgenic mice with Hen egg white lysozime (HEL) or Pigeon Cytochrome-C (PCC) was indistinguishable from immunization of control mice , as judged by recall antigen-induced in vitro proliferation and TCR repert oire analysis, These results indicate that KIR effect on T cells varies upo n cell activation stage and show unexpected complexity in the biological fu nction of KIRs in vivo. (C) 1999 by The American Society of Hematology.