Reconstitution of T Cell Functions in Aging Mice by Thymosin Alpha 1

Helper T cell activity of spleen cells from BDF1 mice is impaired by aging but is restored to a large extent by injection of thymosin alpha 1, a synthetic peptide consisting of 28 amino acid residues. Injection of an equimolar amount of the N14 (N-terminal half of thymosin alpha 1) synthetic fragment is at least as effective as the entire alpha 1 molecule in increasing helper T cell activity of spleen cells from old (6-18 months) mice but not from young (3 months) mice. Conversely, injection of the C14 (C-terminal half of thymosin alpha 1) synthetic fragment is devoid of any effect in both young and old mice. Since helper T cell activity of spleen cells from old mice is also increased by injection of interleukin-2, the observed enhancement of interleukin-2 production by mitogen-activated spleen cells from old mice upon injection of thymosin alpha 1 or the N14 fragment suggests that these peptides amplify helper T cell activity by increasing the cell precursor frequency of interleukin-2-producing T cells. This conclusion is further supported by the finding that injection of thymosin alpha 1, or its N14, but not C14, fragment enhances the expression of interleukin-2 receptors on mitogen-activated spleen cells from old but not from young mice.