CD4+ T CELL MEDIATED DESTRUCTION OF XENOGRAFTS WITHIN CELL-IMPERMEABLE MEMBRANES IN THE ABSENCE OF CD8+ T CELLS AND B CELLS1

Abstract

Xenogeneic cells encapsulated in cell-impermeable diffusion chambers die within 3 weeks when implanted into immunocompetent animals but not when implanted into immunodeficient animals. To determine which cells are necessary for this observation, we depleted normal mice in vivo of either CD4+or CD8+T cells using monoclonal antibodies. We also reconstituted the immune system of athymic CBA mice (T-lymphocyte deficient) and C.B17 SCID mice (T- and B-lymphocyte deficient) with different cell subsets from normal CBA and BALB/C mice, respectively. Depleted or reconstituted mice were implanted with a diffusion chamber containing COS (monkey kidney) cells. Membrane enclosed xenografts survived in CD4+T cell depleted mice but not in CD8+T cell depleted or nondepleted control mice. Encapsulated xenografts survived when implanted into either athymic or SCID mice but were destroyed in reconstituted athymic and SCID mice. Furthermore, encapsulated xenogeneic cells were destroyed in athymic or SCID mice reconstituted with CD4+cell preparations depleted of CD8+cells and/or B cells. In contrast, encapsulated xenogeneic cells were not destroyed in athymic or SCID mice reconstituted with CD8+cell preparations depleted of CD4+cells. These studies highlight the critical role of CD4+T cells, in the absence of CD8+cells and B cells, in the processes leading to the ultimate destruction of encapsulated xenografts. Because of the use of cell-impermeable membranes in these studies, the most likely involvement of CD4+T cells is in the indirect antigen recognition by these cells and subsequent stimulation of inflammatory cells.