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*
R&D Center and
Laboratory Headquarters, BML, Saitama, Japan;
Department of Clinical Pathology, Showa University Fujigaoka Hospital, Kanagawa, Japan;
Department of Clinical Pathology, Juntendo University School of Medicine, Tokyo, Japan;
¶ Department of Microbiology and Immunology, Tohoku University School of Medicine, Miyagi, Japan; and
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Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan
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 infectious diseases. In this study, we identified a novel
secretory protein, killer-specific secretory protein of 37 kDa (Ksp37),
as a Th1-specific protein by a subtractive cloning method between human
Th1 and Th2 cells. In peripheral blood leukocytes, Ksp37 expression was
limited to Th1-type CD4+ T cells, effector CD8+
T cells, 
T cells, and CD16+ NK cells. Most of these
Ksp37-expressing cells coexpressed perforin, indicating that Ksp37 is
selectively and commonly expressed in the lymphocytes that have
cytotoxic potential. Ksp37 was released at constant rate from both
unstimulated and stimulated PBMCs in vitro and also detected in normal
human sera. In healthy 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 counts of
blood T and NK cells between children and adults. In patients with
infectious mononucleosis, transient elevation of serum Ksp37 levels was
observed during the early acute phase of primary EBV infection. These
results suggest that Ksp37 may be involved in an essential process of
cytotoxic lymphocyte-mediated immunity and that Ksp37 may also have
clinical value as a new type of serum indicator for monitoring
cytotoxic lymphocytes in vivo.
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