Mechanism of Action of Prothynosin α 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.

A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes

“…PTMS likely mediates immune function by blocking the effects of prothymosin alpha (50), and reduces the production of IL-2 and IL-2R (IL-2 receptor) required for proliferation of CD4+ T cells (51, 52). As a pro-inflammatory cytokine, IL-2 stimulates lymphocytes, monocytes, lymphokine-activated killer cells, and natural killer cells critical to immune function (53).…”

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

“…Upon analysing the mechanism of action of ProT~ in these in vitro cellular systems, we found that human monocytes after preincubation with ProTo~ (compared to non-treated monocytes) stimulate stronger T lymphocyte 149 proliferation in the mixed-lymphocyte reaction [6], express higher numbers of membrane HLA-DR antigens [7], and present effectively even extremely low amounts of antigen to T cells [6]. Finally, ProTc~ has been shown to increase the production of interleukin-2 and the expression of interleukin-2-specific receptors in antigen-activated T lymphocytes [5].…”

“…I. Gresser [11] were grown in vivo by passage in syngeneic DBA/2 mice as follows. A total of 1.5 ml ascites collected from 3 DBA/2 mice bearing L 1210 was washed twice in phosphate-buffered saline (PBS) and the cell pellet was resuspended in PBS and adjusted to (4)(5)(6)(7)(8)x 105 cells/mi. Three to five DBA/2 mice were then inoculated i. p. with 500 gl of this suspension.…”

The effect of various Prothymosin α fragments on the crystal growth of hydroxyapatite in aqueous solution

“…It is widely distributed in human cells [13], protects against infection from Candida albicans [14], induces the enhanced secretion of interleukin [15] and migration inhibition factor [16], activates monocytes and T-lymphocytes and is a strong immunomodulator [17].…”