The glioblastoma-derived T cell suppressor factor/transforming growth factor-beta 2 inhibits T cell growth without affecting the interaction of interleukin 2 with its receptor.
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.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology*; D007377:Interleukin-3 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016212:Transforming Growth Factor beta; D015291:Transforming Growth Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000494:pharmacology
D007376:Interleukin-2; D007377:Interleukin-3; D010455:Peptides; D010703:Phorbol Esters; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D000001:Calcimycin; D015291:Transforming Growth Factors; D010047:Ovalbumin