A novel serum protein that is selectively produced by cytotoxic lymphocytes

Cytotoxic lymphocytes such as CTL and NK cells play principal roles in the host defense mechanisms. Monitoring these effector cells in vivo is helpful to understand the immune responses in disorders such as cancer and infecti ous diseases. In this study, we identified a novel secretory protein, kille r-specific secretory protein of 37 kDa (Ksp37), as a Th1-specific protein b y a subtractive cloning method between human Th1 and Th2 cells. In peripher al blood leukocytes, Ksp37 expression was limited to Th1-type CD4(+) T cell s, effector CD8(+) T cells, gamma delta T cells, and CD16(+) NK cells. Most of these Ksp37-expressing cells coexpressed perforin, indicating that Ksp3 7 is selectively and commonly expressed in the lymphocytes that have cytoto xic potential. Ksp37 was released at constant rate from both unstimulated a nd stimulated PBMCs in vitro and also detected in normal human sera. In hea lthy individuals, serum Ksp37 levels were significantly higher in children (mean +/- SD; 984 +/- 365 ng/ml for age 0-9) than in adults (441 +/- 135 ng /ml for age 20-99), consistent with reported differences in the absolute co unts of blood T and NK cells between children and adults. In patients with infectious mononucleosis, transient elevation of serum Ksp37 levels was obs erved during the early acute phase of primary EBV infection. These results suggest that Ksp37 may be involved in an essential process of cytotoxic lym phocyte-mediated immunity and that Ksp37 may also have clinical value as a new type of serum indicator for monitoring cytotoxic lymphocytes in vivo.