Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in the popliteal lymph node assay. II. Comparison with acute graft-vs-host reaction in H-2 incompatible F1 mouse hybrids.

Changes in lymphocyte subsets during an acute GVH reaction were compared to STZ-induced PLN response in mice. The GVH reaction was induced locally by sc injection of parental C57Bl/6 [B6] spleen cells into (C57Bl/6 x DBA/2) F1 footpad [B6D2F1]. Early cell activation and time-related changes in T- and B-lymphocyte subsets were monitored during the onset of the GVH reaction by flow cytometry and immunophenotyping. Examination of cell size and chromatin decondensing for T- and B-cell subsets showed differences in activation profile during the early phase of the GVH reaction. The present study provides direct evidence for early in vivo activation of both CD4+ and CD8+ T-cells. Our data confirm the central role of T-cell activation in the induction of a GVH reaction and suggest that recirculatory host B-cells can play an important role in early GVH node enlargement. Overall, our comparative analysis supports the concept of polyclonal T-cell activation for both STZ-related and GVH-induced lymphoproliferation. Chemicals-induced lymphoproliferation leading to autoimmune reactions is a challenging issue. A number of drugs and chemicals have been tested in the PLNA assay for lymphoproliferative potential. We previously reported the activation and proliferation of T-cell subsets following STZ injection into murine footpads. The STZ-induced PLN enlargement and proliferation characteristics of T- and B-cell subsets were postulated to be similar to those of an acute allogeneic GVHR. In the present study, a cytometric analysis of T- and B-cell subsets in PLNs was performed during an acute allogeneic GVHR, for comparison purposes. Such a reaction results in a massive node enlargement five to ten times that seen after stimulation with conventional antigens. Acute GVHR is believed to be a direct consequence of the high frequency of alloreactive donor T-cells inducing a massive proliferation of B-cells, almost exclusively of host origin, in GVHR nodes. It is now widely accepted that donor T-cells activated as the result of exposure to foreign MHC antigens in the recipient, secrete various cytokines which assist the host B-cells and bypass the normal B-T cell cooperation. Induction of an acute GVHR, as in the parental B6--->recipient B6D2F1 model, requires the injection of CD4+ and CD8+ donor T-cells into an F1 recipient that differs from the parent at both MHC class I and II loci.(ABSTRACT TRUNCATED AT 400 WORDS)