Enhancement of helper and suppressor T cell activities by thymosin α1 injection in old mice

Abstract A single injection of immunodeficient old (15–24 month old) BDF1 mice with 1–100 μg of synthetic thymosin α 1 (T α 1 ), a 28-amino acid residue peptide, shortly before horse erythrocyte (HRBC)-priming, enhances the helper activity of their spleen cells. Helper activity of spleen cells from uninjected or T α 1 -injected HRBC-primed old mice was titrated by adding graded numbers of these primed cells to cultures containing a constant number of normal spleen cells from unprimed young (3-month-old) mice and the conjugate 2,4,6-trinitrophenyl (TNP)-HRBC. As evaluated from the in vitro anti-TNP antibody response, spleen cells exhibit higher helper activity when derived from T α 1 -injected, as compared to uninjected, HRBC-primed old mice. No effect is observed when T α 1 is injected in young mice before HRBC-priming. Old mice were also injected with the N 14 (N-terminal amino acid residues 1–14) or the C 14 (C-terminal amino acid residues 15–28) synthetic fragments of the T α 1 molecule. Injection of T α 1 or the N 14 fragment restores the helper activity of old mice to levels comparable to that displayed by helper cells from young mice. Conversely, injection of the C 14 fragment in old mice induces only a negligible increase in helper activity of their spleen cells. T cells from HRBC-primed mice were separated by nylon wool filtration into Th1 (non-adherent) and Th2 (adherent) T cells and these cell subpopulations were assayed for helper activity. Helper activity of Th1 and Th2 cells is found to be impaired by aging when they are tested either separately or upon their recombination. Injection of T α 1 in old mice is able to enhance the helper activity of Th1 and Th2 cells when both subsets are separately tested. Conversely, the decreased helper activity exhibited by Th1 and Th2 cells after their recombination is significantly restored when Th1 but not Th2 cells are derived from T α 1 -injected old mice. It was found that T ga 1 injection in old mice induces Lyt 2 + , nylon wool-adherent, T cells which are able to suppress the helper activity of Th1 and Th2 cells from young or old mice. Nevertheless, enhancement of helper activity is the prevailing effect of T α 1 injection in old mice.