Pro-IL-16 regulation in activated murine CD4+ lymphocytes
Division of Pulmonary and Critical Care Medicine
Animals; CD4-Positive T-Lymphocytes; Calcineurin; Cell Cycle; Cell Proliferation; Female; G0 Phase; Humans; Interleukin-16; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Protein Precursors; RNA, Messenger; Transfection
Circulatory and Respiratory Physiology | Critical Care | Immunology and Infectious Disease
Prior DNA microarray studies suggested that IL-16 mRNA levels decrease following T cell activation, a property unique among cytokines. We examined pro-IL-16 mRNA and protein expression in resting and anti-CD3 mAb-activated primary murine CD4(+) T cells. Consistent with the microarray reports, pro-IL-16 mRNA levels fell within 4 h of activation, and this response is inhibited by cyclosporin A. Total cellular pro-IL-16 protein also fell, reaching a nadir at 48 h. Pro-IL-16 comprises a C-terminal cytokine domain and an N-terminal prodomain that are cleaved by caspase-3. Pro-IL-16 expressed in transfected tumor cells was previously shown to translocate to the nucleus and to promote G(0)/G(1) arrest by stabilizing the cyclin-dependent kinase inhibitor p27(Kip1). In the present study, we observed increased S-phase kinase-associated protein 2 mRNA expression in IL-16 null mice, but basal expression and activation-dependent regulation of p27(Kip1) were no different from wild-type mice. Stimulation with anti-CD3 mAb induced transiently greater thymidine incorporation in IL-16-deficient CD4(+) T cells than wild-type controls, but there was no difference in cell survival or in the CFSE dilution profiles. Analysis of CD4(+) T cell proliferation in vivo using BrdU labeling similarly failed to identify a hyperproliferative phenotype in T cells lacking IL-16. These data demonstrate that pro-IL-16 mRNA and protein expression are dynamically regulated during CD4(+) T cell activation by a calcineurin-dependent mechanism, and that pro-IL-16 might influence T cell cycle regulation, although not in a dominant manner.
Rights and Permissions
Citation: J Immunol. 2005 Mar 1;174(5):2738-45.
Ren, Fucheng; Zhan, Xin; Martens, Gregory W.; Lee, Jinhee; Center, David M.; Hanson, Sue Kim; and Kornfeld, Hardy, "Pro-IL-16 regulation in activated murine CD4+ lymphocytes" (2005). Open Access Articles. Paper 1098.