The glioblastoma‐derived t cell suppressor factor/ transforming growth factor‐β2 inhibits t cell growth without affecting the interaction of interleukin 2 with its receptor

Abstract

Human glioblastoma cells secrete a peptide termed glioblastoma-derived T cell suppressor factor (G-TsF) which inhibits T cell activation. Recently, purification and cloning of G-TsF revealed that G-TsF is identical to transforming growth factor-beta 2. As shown here, G-TsF suppresses the growth of an ovalbumin-specific mouse T helper cell clone (OVA-7T) independently of the stimulus used being either (a) antigen in the presence of antigen-presenting cells, or (b) interleukin 2 (IL2) or (c) phorbol ester and calcium ionophore. Furthermore, in the presence of antibodies against IL2 receptors, G-TsF was able to suppress the residual proliferation still observed when OVA-7T were stimulated with phorbol ester/ionophore. G-TsF failed to inhibit the release of IL3 from OVA-7T activated with IL2. Taken together, the data provide evidence that G-TsF does not directly interfere with interactions of IL2 with its receptor but rather inhibits T cell activation by interfering with an as yet unidentified pathway used by both IL2 and phorbol ester/ionophore. When analyzing different monokines and lymphokines for its effect on G-TsF-induced suppression of T cell growth the only factor found to partially neutralize the effect of G-TsF was tumor necrosis factor-alpha.

Transforming growth factors β1 and β2 as well as milk growth factor decrease anti‐CD3‐induced proliferation of human lymphocytes without inhibiting the anti‐CD3‐mediated increase of [Ca2+]i and the activation of protein kinase C

“…This suggests that the transforming growth factors/~ exert their inhibitory function somewhere 'downstream' of the first events of cell activation. This concept is also supported by the data of Siepl et al [7] and from our laboratory (Stoeck, M. et al, submitted) which show that TGF-/~ interferes with lymphocyte activation induced by a Ca 2+ ionophore and a phorbol ester, a combination which circumvents the respective early events in lymphocyte activation [8]. In addition, IL-2-driven proliferation, which has been shown to be independent of PK-C translocation [9], is inhibited by TGF-/~ [4].…”

Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain

“…Glioma-mediated immunosuppression and downregulation of the host immune response has been associated with the release of immunosuppressive factors by glioma cells, for example, transforming growth factor (TGF)-b1, b2, and b3. [32][33][34][35][36][37][38] In addition to TGF-b, other factors capable of inhibiting immune function 37 include the cytokines interleukin (IL)-6 and IL-10, [39][40][41][42][43][44][45] prostaglandin E, [46][47][48][49][50] and gangliosides. 51 TGF-b1 and IL-10 act by suppressing T cell function.…”

Δ-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway

“…TGF-␤ antagonizes CTL generation (38) and macrophage activities (39,40). The production of TGF-␤ by tumors has been documented as a mechanism of tumor-induced tolerance (41,42). Based on the previously documented detrimental effects of IL-10 and TGF-␤, we speculated that the THC-mediated induction of IL-10 and TGF-␤ could be responsible for enhanced tumor growth in mice receiving THC.…”