Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility.

Gammadelta (gamma delta) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of gamma delta T cells in umbilical cord blood (UCB) is low, and the majority express delta 1, in contrast to blood, whereas the main subset is delta 2 gamma 9 T cells. UCB gamma delta T cells are functionally immature, which together with their scarcity complicates the development of UCB gamma delta T cell therapies. We aimed to develop an effective expansion protocol for UCB gamma delta T cells based on zoledronate and IL-2. We found that culture with 5 mu M zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were gamma 9 delta 2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal gamma delta T cell repertoire and the main memory subset was central memory (CD45RO(+) CD27(+)). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB gamma delta T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.