Processing and release of IL-16 from CD4(+) but not CD8(+) T cells is activation dependent

IL-16 is synthesized as a precursor molecule of 68 kDa (pro-IL-16) that is processed by caspase-3, a member of the IL-1 converting enzyme (ICE) family . This cleavage results in a 13-kDa carboxy terminal peptide, which constit utes the bioactive secreted form of IL-16. We have previously reported cons titutive IL-16 mRNA expression and pro-IL-16 protein in CD4(+) and CD8(+) T cells, Although bioactive IL-16 protein is present in unstimulated CD8(+) T cells, there is no bioactive IL-16 present in CD4(+) T cells. Along these lines, unstimulated CD8(+) T cells contain active caspase-3. In the curren t studies we investigated the regulation of IL-16 protein and mRNA expressi on in CD4(+) T cells and determined the kinetics of secretion following sti mulation of the TCR, CD4(+) T cells release IL-16 protein following antigen ic stimulation, and this release is accelerated in time by costimulation vi a CD28. However, CD3/CD28 costimulation did not alter IL-16 mRNA appearance or stability in either CD4(+) or CD8(+) T cells. The secretion of bioactiv e IL-16 from CD4(+) T cells correlated with the appearance of cleavage of p ro-caspase-3 into its 20-kDa active form, Thus, resting CD8(+) T cells cont ain active caspase-3 that is capable of cleaving pro-IL-16, whereas CD4(+) T cells require activation for the appearance of active caspase-3, The mech anism of release or secretion of bioactive IL-16 is currently unknown, but does not correlate with cellular apoptosis.