Macrophage–T Cell Interaction Is Essential for the Induction of p75 Interleukin 2 (IL–2) Receptor and IL–2 Responsiveness in Human CD4(+) T Cells

Fresh human CD8(+) T cells showed a strong proliferative response to a high concentration of interleukin 2 (IL–2) in the absence of macrophages. In contrast, CD4(+) T cells revealed no significant IL–2 responsiveness in the absence of macrophages. However, if CD4(+) T cells were cocultured with macrophages, they showed higher proliferative response to IL–2 than CD8(+) T cells. In accordance with the magnitude of IL–2 responsiveness, freshly isolated CD8(+) T cells expressed significant amounts of p75 IL–2 receptor, while fresh CD4(+) T cells did not express p75 IL–2 receptor. The expression of p75 IL–2 receptor on CD4(+) T cells was induced by coculture with macrophages. The macrophage–induced p75 IL–2 receptor acquisition was blocked by monoclonal antibody (inAh) against class II antigen. Moreover, the addition of anti–CD4 mAb or anti–class II mAb to the culture caused a great inhibition of IL–2 responsiveness of CD4(+) T cells. These results strongly suggest that macrophage–T cell interaction through CD4 and/or class II molecules is essential for the expression of p75 IL–2 receptor and IL–2 responsiveness in human CD4(+), but not CD8(+) T cells.