Engagement of CD2/LFA-2 on activated human peripheral blood T cells results in an IL-12-dependent resistance to Activation-Induced Cell Death (AICD) in γδ T cells

γδ T cells may play an important role in facilitating hematopoietic engraftment across mismatched MHC barriers in both murine and human bone marrow transplant models. Obtaining suitable numbers of these cells to perform the necessary studies or design clinical trials remains a major problem. Whereas ex vivo expansion of resting γδ T cells would appear to represent an attractive means by which to generate suitable cellular material, here we demonstrate that gammaδ T cells are especially susceptible to the activation-induced cell death (AICD) resulting from in vitro stimulation with a standard T cell mitogenic combination of OKT3 and IL-2. Utilizing Annexin-FITC and propidium iodide (PI) and four-color FACS, we have observed that engagement of CD2/LFA-2 using certain but not all anti-CD2 antibodies generates an IL-12-dependent signal which protects γδ T cells from AICD and results in their preferential expansion in cultures. After 10 days in culture these γδ T cells routinely represent over 50 percent of T cells with expansion of γδ T cells approaching 1,000-fold after 2 weeks. These findings may permit the development of means by which to obtain large numbers of human γδ T cells for use in various forms of adoptive cellular immunotherapy.

Duke Scholars

Author Richard D Lopez Medicine, Hematologic Malignancies and Cellular Therapy