title: Mechanism of action of prothymosin alpha in the human autologous mixed lymphocyte response.
abstract: Prothymosin alpha(Prot alpha), an immunologically active polypeptide derived initially from rat thymus, and now pig thymus, was tested for its effect on autoantigen-induced human T cell proliferation in vitro. Pig ProT alpha was found to enhance the autologous mixed lymphocyte response (auto-MLR). Optimum enhancement was achieved at doses which varied among different donors. Treatment of the stimulatory monocytes with ProT alpha resulted in considerably higher auto-MLR responses as compared to those with non treated monocytes. ProT alpha was without effect on T lymphocytes. In contrast, T lymphocytes exhibited enhanced proliferative activity when treated with ProT alpha in the environment of autologous monocytes. Moreover, supernatants from cultures of monocytes incubated with ProT alpha (ProT alpha-sup) were also shown to enhance the human auto-MLR either after addition in cultures or after preincubation with responder T lymphocytes. In addition, ProT alpha-sup did not demonstrate any detectable interleukin 1 (IL 1) or interleukin 2 (IL 2) - like activity. Furthermore, ProT alpha-sup induced an increase in IL 2 production in auto-MLR cultures. The enhancement of T-cell proliferation and IL 2 production by ProT alpha-sup was maximal when this material was added at the beginning of the auto-MLR, and no effect of ProT alpha-sup was seen if the latter was added 3 days after initiation of the culture. Finally, Prot alpha-sup was also shown to increase the expression of IL 2 receptors on T lymphocytes activated in the auto-MLR. These studies suggest that ProT alpha enhances the human auto-MLR through ProT alpha-sup which is released after interaction of monocytes with ProT alpha ProT alpha-sup then increases directly T lymphocyte proliferation by elevating IL 2 production and expression of IL 2 specific receptors on autoactivated T lymphocytes.
authors.affiliation: Department of Immunology, Hellenic Anticancer Institute, Athens, Greece.
authors.forename: C N
authors.initials: CN
authors.lastname: Baxevanis
authors.forename: G J
authors.initials: GJ
authors.lastname: Reclos
authors.forename: M
authors.initials: M
authors.lastname: Economou
authors.forename: P
authors.initials: P
authors.lastname: Arsenis
authors.forename: A
authors.initials: A
authors.lastname: Katsiyiannis
authors.forename: K
authors.initials: K
authors.lastname: Seferiades
authors.forename: G
authors.initials: G
authors.lastname: Papadopoulos
authors.forename: O
authors.initials: O
authors.lastname: Tsolas
authors.forename: M
authors.initials: M
authors.lastname: Papamichail
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011498:Protein Precursors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin