Terminal Differentiation of Cord Blood Lymphocytes Induced by Thymosin Fraction 5 and Thymosin Alpha₁

Abstract

Cord blood lymphocytes (CBL) have been shown to be functionally immature compared with normal circulating adult lymphocytes (NAL). Differentiation of T cells is associated with changes in surface antigenic markers and in the pattern of purine degradative enzymes. Previous studies have demonstrated that thymosin fraction 5 (TMS-F5) and thymosin alpha 1 (TMS-alpha 1) can induce in vitro differentiation of murine T-cell precursors and human thymocytes. We have investigated the effects of TMS-F5 and TMS-alpha 1 on the pattern of the purine degradative enzymes adenosine deaminase, purine nucleoside phosphorylase, and ecto-5'-nucleotidase (5'NT) of CBL and on the phenotypic markers from the OKT series 3, 4, 8 and 11. Other than a significantly reduced level of 5'NT activity (P less than 0.001) and an elevated percentage of OKT4+ cells (P less than 0.01), CBL demonstrated the same immunological and biochemical patterns as NAL. Incubation of CBL with TMS-F5 (150 micrograms/ml) and TMS-alpha 1 (1 microgram/ml) for 40 h caused a significant rise in 5'NT level and decrease of cells positive for OKT4, resulting in a pattern characteristic of NAL. Thus TMS-F5 might induce the terminal differentiation of CBL, and TMS-alpha 1 seemed to be the active component.

Phenotypic characterization of immature lymphoid cells in human umbilical cord blood

“…In three reports, significant numbers (10-8, 14-2, and 24% of leucocytes) of CD-I + cells were found (7)(8)(9), and the authors cited these findings as indicating the presence of immature T cells in the neonatal circulation. Four other studies, however, documented lower (0-7-2-0%) numbers of these cells (2,6,20,22), a range more consistent with the present observations. The reasons for these discrepancies are presumably methodological.…”

“…metabolites (2), expression of peanut agglutinin receptor (3), reduced formation of rosettes with sheep erythrocytes (4,5), and expression of the stem-cell related antigen detected by monoclonal antibody (Moab) . Significant numbers of cord lymphocytes expressing the immature thymocyte antigen CD-1 detected by Moabs OKT-6 and NAl-34 have also been reported by several groups (7-9).…”

Presence of a peptide component of thymosin fraction-5 manifesting discrete cytostatic properties in HL-60 human promyelocytic leukemia cells

“…Sosne et al [30] reported that Th 4 acts as an anti-apoptotic agent in ethanol-treated human corneal epithelial cells. Notwithstanding these recent findings, however, the capacity of other thymic peptides to oppose cell death may be related to acute induction of differentiation, given that the thymosins promote cellular maturation in normal human lymphocytes [31][32][33][34][35] and stem cells [36]. While the mechanisms underlying anti-apoptotic actions of certain thymosins have not been completely delineated, cytoprotective systems associated with thymosin action include cPKC/nPKC and PKA [25,37] as well as by p125-FAK [28].…”

Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK

“…In fact, Tα1 has been shown capable of increasing lymphocytic infiltration to sites of disease [ 63 , 64 , 65 , 66 , 67 ] while a correlation between tumor-infiltrating lymphocytes and prognosis for patients with stage IV cancer has been documented [ 68 ]. Moreover, Tα1 can reduce apoptosis of immune cells, as shown in mouse [ 69 , 70 ] and human [ 71 , 72 ] thymocytes, and increase stem cell expansion in immunosuppressed mice [ 73 , 74 , 75 ].…”