Correlation of the in vivo and in vitro activities of antithymocyte sera (ATS) with the immunizing antigen dose

Végh, Pál and Erdős, Éva and Jánossy, Tamás and Petri, Gábor (1978) Correlation of the in vivo and in vitro activities of antithymocyte sera (ATS) with the immunizing antigen dose. TRANSPLANTATION, 25 (6). pp. 324-327. ISSN 0041-1337

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Abstract

Rabbits were immunized with I, 3, 10, 30, 100, 300, or 1,000 X 106 murine thymocytes per kg according to the method of Levey and Medawar. Thus, 33 individual and 6 pooled antimouse antithymocyte serum (ATS) preparations were obtained and tested for in vivo immunosuppressive (graft-protective) as well as for in vitro thymocytotoxic activity. It was found that: (1) at least З X 106 thymocytes/kg were necessary for inducing ATS of appreciable immunosuppressive activity; (2) rabbits immunized with 30 x 106 thymocytes/kg supplied sera of the most potent immunosuppressive activity; (3) the increase of the immunizing antigen dose over 30 x 10'' thymocytes/kg resulted in ATS preparations of decreased immunosuppressive activity; (4) the graft-protective activity of an ATS pool corresponded to the average of the activities of the individual ATS preparations from which the pool had been mixed, i.e., the process of pooling itself did not modify the immunosuppressive activity; and (5) there was a good correlation (r = 0.72, P < 0.001) between the in vivo immunosuppressive (graft-protective) activity and the in vitro thymocytotoxic titre ofATS preparations. The theoretical and practical significance of these results is discussed. The method of immunization described by Levey and Medawar (11) is widely acknowledged as a simple and reliable procedure to prepare antilymphocyte serum (ALS). By using this immunization method, it was observed that thymocytes are highly superior either to lymph node or to spleen cells in preparing rabbit anti-mouse ALS of powerful immunosuppressive (graft-protective) activity (15). Furthermore, it has been reported that antithymocyte sera (prepared according to the Levey-Medawar method) are preferable, too, because they produce minimal toxic inflammatory reactions at the site of injection (18). In addition, we found that, by using thymocytes (in contrast to lymph node or spleen cells) as targets in determining the cytotoxic titre of rabbit anti-mouse antispleen, antilymph node, and antithymus sera, there is a very good correlation between the graft-protective activity and thymocytotoxic titre of ALS preparations (17). Thus, having selected a proper immunization method and immunizing antigen, our attention has been focused on the application of the appropriate amount of antigen to produce potent antithymocyte serum (ATS). Another purpose of this study was to determine the correlation of the in vivo graft- protective activity and the in vitro cytotoxic titre of Al’S preparations produced by a wide range of antigen doses.

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