ctin. exp. Immunot. (1990) 80, 360 365 Natural killer activity and antibody-dependent cellular cytotoxicity in progressive systemic sclerosis M. GRAZIA CIFONE. R. GIACOMELL!*. G. FAMULARO*. R. PAOLINIt. C DANESEJ. T NAPOLITANO. A. PROCOPIO. A. M. PEREGO:. A. SANTONI & G. TONIETTI* Departments of E.xperimentat Medicine. * Internat Medicine and Pubtic Heatth. University of L'Aquila. \ Department of Experimental Medicine and XMedieat Ctinie H. University La Sapienza of Rome, Itaty (Accepted for publication 22 January 1990) SUMMARY Enhanced natural killer (NK) activiiy and normal lymphocyte antibody-dependenl cellular cytoloxicity (ADCC) were observed in 16 patients with a diagnosis of progressive systemic sclerosis (PSS). Higher NK activity levels were observed against NK-sensilive K562 target cells, while the NK- rcsistant P8I5, Daudi and Raji cell lines were not lysed. Cytofluorimetric studies and morphological analysis of peripheral blood lymphocytes (PBL) showed an increased number of CD 16 positive cells and large granular lymphocytes (LGL). indicating that the enhancement observed was probably attributable to an increase in the number of circulating NK cells. Keywords progressive systemic sclerosis large granular lymphocytes NK activity ADCC INTRODUCTION Progressive systemic sclerosis (PSS) is a disease of unknown aetiology characterized by connective tissue abnormalities and unexplained over-accumulation of collagen, resulting in fibrosis in the skin and often in the internal organs. The presence of various immunological abnormalities, such as hypcrgammaglo- bulinaemia, circulating autoantibodies. cryoglobulins (Roth- ficldA Rodnan, 1968; Bernstein. Steigerwald & Tan. 1982) and clinical overlapping with diseases such as systemic lupus erythematosus (Kirkland. 1964) have led to the characterization of PSS as an autoimmune disease. The polyclonal activation of B lymphocytes as a major immunologic feature of PSS is also supported by our previous observations ofan increase of both total and activated B lymphocytes concomitantly with higher IgG and IgA levels in the supernatants of peripheral blood lymphocytes (PBL) from PSS patients (Famularo et at., 1989). Several studies suggest that cell-mediated immunity is involved in the pathogenesis of PSS. including decreased total number of T cells, alterations ofT cell subsets, and decreased T cell response to mitogens (Gupta et at., 1979; Inoshita et at., 1981; Whiteside£'r«/.. 1983). Natural killer (NK) cells are CD3-Ti complex negative large granular lymphocytes (LGL) easily identified morphologically by the presence of azurophil granules in their cytoplasm when stained with Giemsa (Timonen. Ortaldo & Herberman, 1981). In humans, they commonly express certain cell surface markers. Correspondence: Dr M. Grazia Cifone, Departmenl of Experi- mental Medicine, University of L'Aquila, Collemaggio, 67100 L'Aquila, Italy. such as CDt6 (Fc receptor III) (Perussia et at.. 1984) and CD56 (NKH-1) (Griffin et at.. 1983; Lanier et at.. 1986). NK cells appear to play a leading role in host defense against tumours and viral infection, as shown in many experimental systems (Herberman. 1982). They mediate non-MHC-restricted cytoly- lic reactions without prior sensitization and are the main cellular effectors of antibody-dependent cell cytotoxicity (ADCC) through the expression of low affinity IgG-specific Fc receptors (CD 16) (Herberman et at., 1979; Bolhuis, 1980). They also mediate antigen presentation (Scala et at.. 1985) and are involved in the B cell responses (Arai et at., 1983; Abbruzzo, Mullen & Rowley. 1986; Kuwanoe/n/., 1986; Robles& Pollack. 1986). Involvement of NK cells in the pathophysiology of PSS has been suggested, although both diminished and enhanced re- sponses have been reported (Wright, Hughes & Rowell, 1982; Valentini c/«/.. 1984; Freundlich& Jimenez, 1987; Majewski e/ at.. 1987; Miller ff (7/., 1988). In this study, we have investigated both NK cell number and activity (natural killing and ADCC) in an homogeneous group of PSS patients with mild progression and a duration of disease > 7 years (max. 30 years). MATERIALS AND METHODS Patienis and controts The patients were 16 women ranging in age from 28 to 67 years (mean age 57 7 years) diagnosed according to the criteria of the American Rheumatism Association for diffuse PSS (Masi el at.. 360 Downloaded from https://academic.oup.com/cei/article/80/3/360/6490497 by guest on 19 July 2023