Immunopharmacology, 8 (1984) 69-11 Elsevier 69 IMO 00242 Specific II. Age-Associated Antibody Synthesis In Vitro. Thymosin Enhancement of Antitetanus Antibody Synthesis William B. Ershler’, Ann L. Moore’, Miles P. Hackerl, James Ninomiya’, Paul Naylo? and Allan L. Goldstein2 ‘Departments of Medicine and Pharmacology, Vermont Regional Cancer Center, University of Vermont, 1 South Prospect Street. Bur- lington, VT 05401. U.S.A. and =Department of Biochemistry, George W ashingron University School of Medicine and Health Sciences (Received 17 February 1984; accepted 19 June 1984) Abstract: A decline in T cell function accounts for many of the observed age-related deficient immune responses. Specific antibody response to many antigens requires T cell cooperation, and deficient antibody response to such antigens has been demonstrated with aging. In an effort to assess the potential reconstitutive capacity of Thymosin Fraction 5, in vitro antitetanus antibody production was measured in tetanus toxoid booster-immunized young and old volunteers. 22 young and 12 old volunteers were immunized with tetanus toxoid and plasma antitetanus antibody and in vitro lymphocyte production of antitetanus antibody was measured. Plasma antitetanus antibody response was significantly greater in the young. In vitro antitetanus antibody synthesis was negligible prior to immunization and peaked in cultures established 1 week after immunization from both young and old. When Thymosin Fraction 5 was added to the cultures, however, there was a dose-related enhancement of antibody synthesis in 7 of 10 from the group of elderly volunteers, but only 3 of 12 from the younger group. Our data indicate that specific antibody response is deficient in the elderly, but can be enhanced in vitro by thymosin. A future clinical trial of thymosin as an adjuvant to active immunization for the elderly is warranted. Key zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA words: Aging and immunity: Immunosenescense; Immune reconstitution; Specific antibody synthesis; Thymosin Introduction Infectious diseases continue to exert considerable morbidity and mortality upon the elderly popula- tion (Kohn, 1982; Haleen, 1982). Otherwise effec- tive immunization programs may be thwarted by an age-related inadequate response to immunogen- ic challenge. The immune deficiency associated with aging involves primarily T cell functions and in- cludes the antibody response to certain T cell-de- pendent antigens (Callard and Basten, 1982). Al- though the production of specific antibody in re- sponse to antigen is considered a humoral or B cell response, it is currently believed that for most pro- tein antigens the IgG response is regulated by T cell 0162-3109/84/$03.00 0 1984 Elsevier Science Publishers B.V. factors (Willox, 1975). In an effort to determine whether augmentation of T cell functions by a thymic hormone preparation might influence anti- body response in the elderly, we studied specific and nonspecific antibody synthesis in vivo and in vitro in response to tetanus toxoid booster immunization in normal young and elderly volunteers. Whereas plasma antitetanus levels were greater post immu- nization in the younger group, the augmentation of in vitro specific antibody synthesis by thymosin was Abbreviaiions: TT, tetanus toxoid; PBS-T, phosphate buffered saline-Tween; ELISA, enzyme-linked immunosorbent assay; MASELA, microculture antibody synthesis enzyme-linked as- say; TF5, Thymosin Fraction 5.