LYMPHOTACTIN IS PRODUCED BY NK CELLS AND ATTRACTS BOTH NK CELLS AND T-CELLS IN-VIVO

Injection of lymphotactin (Lptn) into the peritoneum caused an influx of lymphocytes at 24 h, Phenotypic analysis of the cellular influx sho wed that a large proportion of these cells were T lymphocytes; however , a large number of NK cells was also present, This effect of murine L ptn (mLptn) was specific since the cellular influx was blocked with a mLptn-specific mAb. Similar results were observed when Lptn was inject ed s.c. and the tissue was analyzed by immunohistochemistry using an a nti-CD3 epsilon mAb, Microchemotaxis assays confirmed that murine NK c ells respond to mLptn, and also showed human NK clones to be similarly responsive to recombinant human Lptn (rhLptn). Immunohistochemical an alysis oi IL-2-activated murine NK cells and Northern analysis of huma n NK clones revealed that these cells also produce Lptn, suggesting th at a self-regulatory migration mechanism exists in NK cells. Together these data confirm, in vivo, the lymphocyte specificity of Lptn previo usly observed in vitro and extend its chemotactic effects to the NK ce ll lineage, We also investigated the functional consequences of trunca ting the carboxyl terminus of hLptn, This truncated molecule (which is missing the carboxyl-terminal 22 amino acids of hLptn) had no detecta ble activity on human PBLs, In addition, while hLptn was found to attr act murine splenocytes in vitro, the carboxyl-terminal truncated hLptn was again inactive on murine splenocytes. This observation indicates the presence of structural features in the carboxyl terminus of Lptn t hat are necessary for its biologic activity.