Transplant Immunology 12 (2004) 103–108 0966-3274/04/$ - see front matter  2003 Elsevier B.V. All rights reserved. doi:10.1016/j.trim.2003.11.002 Correlation between interleukin-15 and granzyme B expression and acute lung allograft rejection Ruili Shi , Junbao Yang , Andres Jaramillo , Nancy S. Steward , Aviva Aloush , Elbert P. Trulock , a a a a a b ´ G. Alexander Patterson , Manikkam Suthanthiran , T. Mohanakumar * a c,d a,e, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA a Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA b Division of Nephrology Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA c Department of Transplantation Medicine, New York Presbyterian Hospital, New York, NY 10021, USA d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA e Received 26 June 2003; received in revised form 29 October 2003; accepted 6 November 2003 Abstract The levels of interleukin (IL)-15 and granzyme B mRNA expression have been correlated with acute rejection episodes of kidney and heart allografts. Thus, the purpose of this study was to determine whether a correlation exists between the expression of IL-15 and granzyme B and acute lung allograft rejection. Toward this, the levels of IL-15 and granzyme B mRNA expression were determined in bronchoalveolar lavage-derived alveolar macrophages and total cells, respectively, from lung transplant patients with stable lung allograft function and patients undergoing acute rejection episodes. The expression levels of IL-15 mRNA was significantly higher in the patients undergoing acute rejection as compared to patients with stable lung function (Ps0.02). The expression levels of granzyme B mRNA was also significantly higher in the patients undergoing acute rejection as compared to patients with stable lung function (Ps0.005). The Receiver–Operating–Characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 94% and specificity of 67% with the use of a cutoff value of 3.1 fg of granzyme B mRNA per microgram of total RNA (or 71% sensitivity and 75% specificity of a cutoff value of 9.1 fgymg). These data indicate that IL-15 secreted by activated alveolar macrophages and granzyme B secreted by activated CD8q cytotoxic T lymphocytes play important roles in the process of acute lung allograft rejection.  2003 Elsevier B.V. All rights reserved. Keywords: Lung transplantation; Acute allograft rejection; Granzyme B; Interleukin-15 1. Introduction Lung transplantation is a valid therapeutic option for a variety of end-stage pulmonary disease. However, the loss of graft function due to the development of bron- chiolitis obliterans syndrome, considered to represent chronic lung allograft rejection, continues to be a chal- lenge to the long-term success of lung transplantation. Since acute lung allograft rejection is a major risk factor for the development of bronchiolitis obliterans syn- drome, the prompt diagnosis and treatment of acute lung allograft rejection is essential w1,2x. Better understanding of the immunological mechanisms that underlie the *Corresponding author. Tel.: q1-314-362-8463; fax: q1-314-747- 1560. E-mail address: kumart@wustl.edu (T. Mohanakumar). process of lung allograft rejection will benefit for its diagnosis and management. T cells are of central importance in the execution of allograft rejection. This process involves the activation of both CD4q and CD8q T cells. The activation of T cells starts with the interaction of the specific alloantigen presented by antigen presenting cells such as macro- phages and the T cell receptor (signal 1). Additional signals are needed to fully activate the T cells, which include T cell co-stimulation (signal 2) and T cell growth factors (signal 3) such as interleukin (IL)-2, IL- 4, IL-7, IL-9, IL-15, and IL-21 w3,4x. Among these cytokines, IL-15 uses the beta and gamma subunits of the IL-2 receptor and shares several biological activities with IL-2 w4–6x. IL-15 induces T cell proliferation and chemotaxis, B cell maturation, and natural killer cell