The proliferative reactivity of lymphocytes from rat donors maintained under germfree or conventional conditions was examined in mixed lymphocyte cultures stimulated with allogeneic and xenogeneic cell surface antigens. The results show (a) that lymphocytes from conventionally maintained rats are less reactive to human, hamster, guinea pig, and mouse cell surface antigens than to the major H alloantigens, and (b) that lymphocytes from germfree rats display no demonstrable reactivity to xenogeneic cells, but are quantitatively normal in their response to allogenic cells. The conclusion drawn from these observations is that the circulating lymphocyte pool of an individual consists of a greater proportion of cells reactive to H alloantigens of other members of the same species than to the xenogeneic cellular antigens of members of other species and that this large number of cells is not generated by a mechanism involving immunization to cross-reactive environmental antigens.

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