Lymphocytotoxicity and immunosuppression by organotin compounds. Suppression of graft-versus-host reactivity, blast transformation, and E-rosette formation by Di-n-butyltindichloride and Di-n-Octyltindichloride

Abstract

Di-n-butyltindichloride (DBTC) and di-n-octyltindichloride (DOTC) represent a new group of organometallic compounds with antilymphocytic properties. In rats they induce lymphocyte depletion in thymus and thymus-dependent areas of spleen and peripheral lymph nodes without signs of myelotoxicity or a generalized toxicity. The number and viability of cells isolated from thymus and peripheral lymphoid organs was severely decreased, whereas the number and viability of bone marrow cells was not reduced. Immunosuppressive properties of DBTC and DOTC are indicated, in this study, by a severe decrease of the graft-versus-host response and the response to the T-cell mitogens phytohemagglutinin and concanavalin A. The T-cell selectivity of these compounds is discussed. In vitro DBTC and DOTC are extremely cytotoxic. Blast transformation of human as well as rat thymocytes was already inhibited at concentrations as low as 0.02 μg DBTC (or 0.1 μg DOTC) ml medium. Also the E-rosette formation was inhibited at very low drug levels. The similarity of effects upon rat and human lymphocytes suggests that DBTC and DOTC acts in the same manner in rat and man and offers the possiblity of a therapeutic use of these compounds.