Cutting edge: CD4 is not required for the functional activity of IL-16

IL-16 functions as a chemoattractant factor, inhibitor of HIV replication, and inducer of proinflammatory cytokine production. Previous studies have s uggested that CD4 is:the receptor for IL-16, because only CD4(+) cells resp ond to IL-16 and both the anti-CD4 Ab OKT4 and soluble CD4 can block IL-16 function. However, these are only indirect evidence of a requirement for CD 4, and to date a direct interaction between IL-16 and CD4 has not been show n. In this paper, we report that cells from CD4 knockout mice are as respon sive to IL-16 as their CD4 wild-type equivalents in both assays testing for IL-16 function (chemotaxis and production of proinflammatory cytokines), I n addition, the inhibitory effect of soluble CD4 on IL-16 function observed using CD4 wild type murine cells was not observed using CD4 knockout cells , These data demonstrate that CD4 is not required for IL-16 function and su ggest that another molecule acts as the major receptor.