Immunology Letters 50 (1996) 51-57 Dimethyl sulfoxide induces programmed cell death and reversible Gl arrest in the cell cycle of human lymphoid pre-T cell line Oriana Trubiani”, *, Marina Ciancarellib, Monica Rapine”, Roberto Di Primiod “Istituto di Moyfblogia Umana Normale, Facoltri di Medicina, Universitci di Chieti. Via dei Vrstini 12. h6lW (‘lriet~. Ittrl\. bServizio di Immunoematologia ULSS 1 I Pescara, Ital? ‘Istituto di Citomorfologia Normale e Patologica de1 CNR, 66100 Chieti. Ital), ‘Istituto di Morfologia Umana Normale, Unicersitci di Ancona. 40123 Ancona. Ita!, Received 29 November 1995; revised 9 February 1996: accepted 14 February 1996 Abstract In human B- and T-differentiated lymphoid cell lines DMSO was found to arrest the proliferation at the Gl stage of the cell cycle, without any detectable differentiation and DMSO itself was found to prevent apoptosis. Programmed cell death, or apoptosis, is now thought to be an important regulatory process in normal hemopoiesis and in the lymphoid system this program is started in the immune process such as autoreactive T-cell elimination in the thymus, and antigen-driven B-cell selection in the germinal centre. For this purpose, we have analysed the effect of DMSO using undifferentiated pre-B (KM-J) and pre-T (RPMI-8402) human lymphoid cells. Results obtained by multiparametric analyses show that DMSO affect only the pre-T cell line inducing a reversible Gl arrest of the cell cycle with a significant presence of apoptotic cells and modification of terminal transferase (TdT) expression. Pre-B cell line is resistant to DMSO treatment. These data provide evidence of a new model for the study of the selective cell type depending effect of DMSO in the immune system. Ke_word.s: DMSO; Cell cycle; Apoptosis; Lymphoid cell 1. Introduction Cell death takes two different main forms, necrosis and apoptosis, which differ in morphology, biochem- istry, incidence and biological significance [ 1 - 31. Necro- sis is a pathological event associated with the cessation of the synthetic function; the latter is apparently a regulated event dependant upon an active metabolism and protein synthesis by dying cells. Apoptosis or pro- grammed cell death has long been known to be a fundamental feature of the development of multicellular organisms and to occur in many adult tissues undergo- ing regression or remodelling [4-61. In the immune system apoptosis is thought to mediate both the clonal deletions of ineffective T and B cells during the differen- tiation process [7-lo]. Immature T and B lymphocytes * Corresponding author. Tel.: + 39 871 563541: fax: + 39 871 574361. undergo a programmed series of differentiation events before emerging into the periphery as competent T and B cells. The differentiation is intrinsically learned and the production of mature lymphoid cells within the bone marrow and lymphoid organs is regulated by a range of growth factors. During the differentiation pro- cess, immature lymphocytes could enter a committed phase and many apoptotic signals begin the final execu- tion phase necessary for the elimination of the ineffec- tive lymphocyte subpopultations by the intrinsic programme of cell death. Extensive apoptosis in rapidly proliferating normal cell populations, lymphoid tissues and tumours is induced by a variety of cytokines, growth factors, hormones, drugs and biochemical agents, one of these is the dimethyl sulfoxide (DMSO) [l l- 131. DMSO typically promotes the cell differentia- tion and its ability is associated to growth-arrest cells at the GO/G1 phase of the cell cycle [ 14 201. In other experimental conditions rather than terminal differenti- ation DMSO provokes the programmed cell death 1211. 0165-2478/96/$12.00 0 1996 Elsevier Science B.V. All rights reserved PII SO 165-2478(96)025 IS-7