The effects of heterologous anti-thymocyte sera in mice. III. High susceptibility of germfree mice to the suppressive effects of IgG from rabbit anti-mouse thymocyte serum

Abstract

A quantitative graft-vs.-host (GVH) assay was used to compare the reactivity of spleen cells from germfree (GF) and conventionally reared (CV) mice against allogeneic tissue before and after treatment with rabbit anti-mouse thymocyte serum (ATS) and its IgG fraction (AT-IgG). AT-IgG produced a far greater and longer lasting suppression of this reactivity in GF than in CV mice. Moreover, CV mice recovered from suppression twice as rapidly as did GF mice. In both groups, the rate of recovery was exponential. These results suggest that recovery from the suppressive effects of ATS or AT-IgG was the result of generation of new cells. Transfer of mice born and initially reared in a conventional animal room to germfree isolators, with subsequent maintenance on the same diet that the germfree mice received, did not change the reactivity of their spleen cells in the assay used nor their susceptibility to AT-IgG. Removal of GF mice to a conventional animal room resulted in a prompt reduction in susceptibility to AT-IgG. The possibility that this might be related to the elaboration of a plasma factor affecting lymphocyte stability was discussed. Spleen cells taken from GF mice at various times after such conventionalization showed a transient but marked hyperreactivity to tissues of the allogeneic recipients. The amount of reduction in reactivity of spleen cells from such mice treated with AT-IgG was always proportional to the activity of spleen cells from comparable untreated mice. It was suggested that the increased reactions evoked should be ascribed to an adjuvant effect rather than to specific immunologic sensitization. Blood lymphocyte counts correlated very poorly with the state of suppression, confirming previous observations. It was also shown that while AT-IgG had little or no effect on blood granulocyte counts in both GF and CV mice, marked reductions in circulating granulocytes followed administration of AT-IgG during the period of increased granulocytopoiesis that resulted from conventionalization. This demonstrated that AT-IgG can produce functional impairment of target cells other than lymphocytes.