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

Xenogeneic cells encapsulated in cell-impermeable diffusion chambers d ie within 3 weeks when implanted into immunocompetent animals hut not when implanted into immnunodeficient animals. To determine which cells are necessary for this observation, we depleted normal mice in vivo o f either CD4(+) or CD8(+) T cells using monoclonal antibodies, We also reconstituted the immune system of athymic CBA mice (T-lymphocyte def icient) and C.B17 SCID mice (T- and B-lymphocyte deficient) with diffe rent cell subsets from normal CBA and BALB/C mice, respectively. deple ted or reconstituted mice were implanted with a diffusion chamber cont aining COS (monkey kidney) cells. Membrane enclosed xenografts survive d in CD4(+) T cell depleted mice but not in CD8(+) T cell depleted or nondepleted control mice. Encapsulated xenografts survived when implan ted into either athymic or SCID mice but were destroyed in reconstitut ed athymic and SClD mice. Furthermore, encapsulated xenogeneic cells w ere destroyed in athymic or SCID mice reconstituted with CD4(+) cell p reparations depleted of CD8(+) cells and/or B cells. In contrast, enca psulated xenogeneic cells were not destroyed in athymic or SCID mice r econstituted with CD8(+) cell preparations depleted of CD ai cells. Th ese studies highlight the critical role of CD4(+) T cells, in the abse nce of CD8(+) cells and B cells, in the processes leading to the ultim ate destruction of encapsulated xenografts. Because of the use of cell -impermeable membranes in these studies, the most likely involvement o f CD4(+) T cells is in the indirect antigen recognition by these cells and subsequent stimulation of inflammatory cells.