Cryopreservation-induced enhancement of interleukin-2 production in human peripheral blood mononuclear cells

Abstract

To better understand the effects of cryopreservation on various immunocompetent cell functions, we have examined the interleukin-2 (IL-2)-producing activities of frozen mononuclear cells (MNCs) from healthy subjects. The mechanisms responsible for the observed effects were also analyzed. Both the unfractionated and monocyte-depleted, frozen MNCs produced significantly larger quantities of IL-2 than fresh cells. Similar to freezing, l-leucine methyl ester (Leu-OMe) treatment (to eliminate IL-1 and prostaglandin E-2 (PGE-2)-secreting cells) also increased the IL-2-producing activities of fresh cells, but freezing no longer enhanced the production of IL-2 by Leu-OMe-treated cells, suggesting that (1) both the freezing process and Leu-OMe treatment have similar effects on IL-2 production, (2) the increased IL-2 secretion by frozen MNCs is independent of IL-1, and (3) inactivation of PGE-2-secreting cells during the freezing procedure is responsible for increased IL-2 secretion. Elimination of CD8 + T cells (putative suppressor cells) from MNCs has also resulted in the production of increased amounts of IL-2 by fresh cells, and again, freezing did not further enhance the IL-2-secreting activities of MNCs, that are devoid of CD8 + T cells. This confirms that the increased IL-2 production is due to the inactivation of immuno-down-regulatory cells. The results provide further evidence that the lack of active, suppressor T cells, monocytes, and increased IL-1 and -2 production may be responsible for the previously reported enhanced immunoglobulin-producing abilities of cryopreserved cells from healthy subjects and from patients with lung cancer.