Stimulation of DNA Synthesis in Bovine Leukocyte Cultures by Trypanosoma theileri Antigen

Abstract

Preliminary studies of the in vitro stimulatory effect of T. theileri antigen on the peripheral blood mononuclear leukocytes of 24 cattle, as measured by the incorporation of thymidine-methyl-H3 into trichloracetic acid precipitable material are reported. Seven animals gave a positive response, 4 gave a doubtful response, and 13 gave no response. This indicated that the peripheral blood mononuclear leukocytes of some cattle are able to respond in vitro to T. theileri antigen. No correlation between trypanosome infection, as determined by blood culture, or lymphocytosis status of the animal and the response to trypanosome antigen was evident. Trypanosoma theileri infection is generally considered to be nonpathogenic, though in the USA it has been associated with depressed milk production (Ristic and Trager, 1958) and abortion in cattle (Levine et al., 1956). However, in view of its ubiquitous distribution (Herbert, 1964; Leach, 1966; Wells et al., 1965) it is likely that the organism will be found in association with many clinical disease entities. Its association with leukemict cattle was reported by Malmquist (1965) and by Cross et al. (1968). Our own studies have indicated that T. theileri infection is widespread in cattle in Pennsylvania, with a high frequency in leukosis (leukemia)t and lymphocytosist herds, as well as leukosis (leukemia)freet herds (to be published). In addition, we have observed that the mitotic index of bovine peripheral blood leukocyte cultures is frequently higher when trypanosomes are present than when they are absent (Hare et al., 1967). Though little is known of the changes in the lymphoid elements as a consequence of T. theileri infection, it was felt that a further investigation of the relationship of the protozoan infection to bovine persistent lymphocytosis and leukemia was warranted, since an apparent relationship between another blood protozoan (Babesia) and bovine persistent Received for publication 31 December 1968. * This work was supported by U. S. Public Health Service Grants AI-06262, FR-00120, and CA06352. t Terms used as defined or recommended in Criteria for the Determination of the Normal and Leukotic State in Cattle prepared by Internation Committee on Bovine Leukosis (Marshak, 1968). lymphocytosis and leukemia has been reported (Olson, 1961; Bodin et al., 1961). More recently, Burkitt (1969) has suggested that chronic malarial infection may predispose the reticuloendothelial system of man to tumor formation in Burkitt's lymphoma. If, for example, it could be demonstrated that T. theileri can cause stimulation of leukocytes in vitro, then it might be postulated that the protozoan could have a similar effect on the lymphopoietic system in vivo. Furthermore, to our knowledge there has been no work on the stimulation of leukocytes in vitro by protozoan antigens. This report gives the results of preliminary studies on the in vitro stimulatory effect of T. theileri antigens on the peripheral blood mononuclear leukocytes of cattle, as measured by the incorporation of radioactive thymidine into trichloracetic acid precipitable material. MATERIALS AND METHODS