Signal mechanisms for synergistic effects of IL-2 and CD2 crosslinking on NK cell proliferation

Abstract

Since infiltration of T cells and natural killer (NK) cells is observed in inflammatory gingival tissues, local immunoresponse is believed to be involved in periodontal diseases.I investigated costimulatory effects of CD2 stimulation on IL-2-mediated NK cell proliferation and signal pathways through CD2 and IL-2 using the NK cell line, NK3.3. Costimulation of CD2 crosslinking significantly enhanced IL-2-mediated NK3.3 proliferation.Crosslinking of CD2 induced tyrosine phosphorylation of protein tyrosine kinase, Syk and the adapter proteins, Shc and Cbl. However, IL-2 stimulation enhanced tyrosine phosphorylation of Shc, but not Syk nor Cbl. Cbl constitutively associates with Grb 2 through the N-SH3 domain, whereas Shc associates with Grb2 through the SH2 domain in an activation-dependent manner.