Int. J. lmmunopharmac., Vol. 8, No. 7, pp. 667-676, 1986. 0192-0561/86 $3.00+ .00 Printed in Great Britain. International Society for [mmunopharmacology. THYMOSIN al AND THYMOSIN/34 IN SERUM: COMPARISON OF NORMAL, CORD, HOMOSEXUAL AND AIDS SERUM PAUL H. NAYLOR,* ALVIN FRIEDMAN-KIEN t EVAN HERSH,* MICHAEL ERDOS* and ALLAN L. GOLDSTEIN* *Department of Biochemistry, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037; *Department of Dermatology, New York University Medical Center, New York, NY 10016 and *Department of Clinical Immunology, M.D. Anderson Tumor Institute, Houston, TX 77030, U.S.A. (Received 8 March 1985 and in final form 11 December 1985) Ahstrac! -- Thymosin a~ and thymosin f14 were first isolated from thymosin fr. 5 and have demonstrated biological activities on the immune system. They are chemically distinct and differ in their immunological activity profiles. The levels of thymosin a~ and thymosin/L were assessed by radioimmunoassay in the same serum samples. Normal thymosin a~ levels were 670 _+163 pg/ml for males and 652 _+162 pg/ml for females. Normal thymosin/34 levels were 974 _+ 400 ng/ml for males and 889 +_ 345 ng/ml for females. No correlation between the levels of the peptides in serum from normal donors was observed. Although many samples of serum from neonates (cord blood), homosexuals and AIDS patients had elevated levels of one or both peptides, no correlation between the two peptides was found. Of potential significance is the observation that while thymosin al and f14 are elevated in many individuals with AIDS (57 and 48% respectively), the individuals with AIDS related immune dysfunctions had predominantly elevated thymosin al (54 vs 15%). These studies suggest that serum levels of the two peptides are modulated separately and that both are of potential value in defining the risk of individuals for developing AIDS. Investigations over the last two decades have confirmed that the development of T cell immunity requires a properly functioning thymus and that thymic polypeptides are mediators of the differentiation of precursor lymphocytes into mature thymus derived lymphocytes (T cells) (reviewed in White & Goldstein, 1975; Goldstein, Low, Zatz, Hall & Nayior, 1983). Thymic hormones have also been identified in the blood, confirming the endocrine nature of the thymus and suggesting both an intra- thymic and extra-thymic role for the thymic peptides (Goldstein et al., 1983). The most extensively studied thymus gland preparation, thymosin fraction 5 (TF5) was described by Hooper, McDaniel, Thurman, Cohen, Schulof and Goldstein (1975). To date, 11 of the 40-50 peptides in TF5 have been isolated and biochemically characterized (Goldstein et aL, 1983). Two of these peptides, thymosin al and thymosin/L, have been sequenced and synthesized (Goldstein, Low, McAdoo, McClure, Thurman, Rossio, Lai, Change, Wang, Harvey, Ramel & Merenhofer, 1977; Low, Hu & Goldstein, 1981). Using a heterologous rabbit antibody, thymosin al, has been localized by indirect immunofluorescence to epithelial cells in the thymic subcortical capsule and the medulla (Kater, Oosterman, McClure & Goldstein, 1979; Hirokawa, McClure & Goldstein, 1982, Dalakas, Rose, Paul, Engle, McClure & Goldstein 1983; Haynes, Robert° Guroff, Metzgar, Franchini, Kalyanaraman, Palker & Gallo, 1983). In a similar manner thymosin/~4 has been localized to the thymic subcortical capsule epithelial cells (Goldstein, Low, Thurman, Zatz, Hall, Chen, Hu, Naylor & McClure, 1981). Thymosin al (mol. wt = 3108) is active in a wide spectrum of in vitro and in vivo assays of T cell differentiation and function. (Goldstein et al., 1977; Low et al., 1981; Goldstein et al., 1983). Biological properties of thymosin a~ include induction of T cell markers, stimulation of the production of Address correspondence to: Dr. Paul H. Naylor, Department of Biochemistry, The George Washington U, 2300 Eye St., N.W., Washington, DC 20037, U.S.A. 667