Immunology Letters 74 (2000) 111 – 115 Ehrlich ascites tumour unbalances splenic cell populations and reduces responsiveness of T cells to Staphylococcus aureus enterotoxin B stimulation Juan A. Segura *, Laura G. Barbero, Javier Ma ´rquez Departamento de Biologı ´a Molecular y Bioquı ´mica, Facultad de Ciencias, Uniersidad de Ma ´laga, 29071 Ma ´laga, Spain Received 22 March 2000; received in revised form 4 June 2000; accepted 4 June 2000 Abstract Tumours must avoid host immune response to survive and proliferate; to achieve this purpose, tumours interact with cells of the immune system by means of tumour secreted factors. The alterations of splenic cell populations in mice bearing the Ehrlich ascites tumour have been studied. A rapid and acute response was observed, characterized by a decrease in both CD4 and CD8 T cells, and a transient increase in the number of B cells, which peaked 2 days after tumour inoculation. An increase in macrophage population and in the homing antigen CD18 was also detected. In vitro incubations of splenic cells with the Staphylococcus aureus enterotoxin B (SEB) showed that tumour induces a state of reduced responsiveness to stimulation of T cells, mainly affecting CD8 T cells, and a diminished IFN- expression. © 2000 Elsevier Science B.V. All rights reserved. Keywords: Ehrlich ascites tumour; Spleen; Immune response; Staphyloccocus aureus enterotoxin B www.elsevier.com/locate/ 1. Introduction Ehrlich ascites tumour is a rapidly growing car- cinoma with very aggressive behaviour. It is charac- terized by a high rate of glutamine consumption [1], by secreting a variety of immunosuppressive cytokines [2,3] and by a lack of class II MHC expression [4]. These events result in a dysfunction of T and NK cell immunosurveillance [5 – 7] and in the recruitment of suppressive macrophages [5]. Notwithstanding, Ehrlich ascites cells are clearly immunogenic since mice inocu- lated with attenuated tumour cells are capable of ac- tively recognizing them as foreign, and acquire a memory that will reject a second inoculation of live Ehrlich ascites tumour cells [8]. In recent studies on Ehrlich ascites tumour model [9], our group has found early tumour effects on Th lymphocytes of the host, accounting for a dramatic decrease in the number of Th cells in the spleen of tumour-bearing mice 2 days after tumour inoculation. This decrease is accompanied with a reduction in the number of CD4 cells expressing IFN- after in vitro polyclonal stimulation with PMA and ionomycin. Since host immune responses to tumour antigens are weak and not immediate [10], the early contacts between host and tumour are critical in determining the future directions of the immune response elicited by tumour antigens. We have recently demonstrated the presence of TGF-1 in the tumour cells and ascites of tumour-bearing mice [9]. The lack of func- tional receptors [11] allows tumour cells to avoid the potent growth inhibitory effects of TGF- on itself and to send an inhibitory signal to the immune sys- tem [12]. In this work, we intended to extend the study of the tumour-induced changes in the number of the different splenic cell populations. Furthermore, the responsive status of T cells during the first days of tumour growth was undertaken using SEB. This closely resembles the physiologic activation pathway of T cells, and allowed us to assess the presence of tumour signals that inhibit the immune system re- sponse. * Corresponding author. Tel.: +34-95-2132024; fax: +34-95- 2132000. E-mail address: jsegura@uma.es (J.A. Segura). 0165-2478/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII:S0165-2478(00)00208-X