Search

Abundant evidence suggests that Treponema pallidum (T.p.) escapes humoral immune defence despite the host produces antibodies early in the infection. Since the serologic responses in syphilis have been studied in detail this paper focuses on the cellular immune mechanisms. For this purpose the leukocyte migration inhibition was investigated in 17 patients in different stages of syphilis. Leukocyte migration inhibition assay was performed before, and 7 days, 3 weeks, 2 mo, and 1 yr after start of treatment. Ultrasonicated T.p. were used as antigen corresponding to 5 × 106 to 2 × 107 Treponema pallida per ml. Controls without antigen, with addition of Concanavalin A instead of T.p. and using cells of normal volunteers were run. There was no leukocyte migration inhibition before treatment, suggesting nonexistent or depressed cellular immunity in the untreated syphilitic patient. Significant leukocyte migration inhibition, however, was observed as early as 2 days after start of treatment, being most pronounced after 1 week. Hypothetical circulating blocking factors for cellular immune reactions might be present in the untreated syphilitic patient, which become abolished after therapy. Since stimulation with Con A of syphilitic leukocytes gave normal results even before treatment in the syphilitic patient, there might be a specific block of leukocyte migration inhibition against T.p. [ABSTRACT FROM AUTHOR]

Hedgehog signaling is often activated in tumors, yet it remains unclear how GLI2, a transcription factor activated by this pathway, acts as an oncogene. We show that GLI2 is a pleiotropic oncogene. The overexpression induces genomic instability and blocks differentiation, likely mediated in part by enhanced expression of the stem cell gene SOX2. GLI2 also induces transforming growth factor (TGF)B1-dependent transdifferentiation of foreskin and tongue, but not gingival fibroblasts into myofibroblasts, creating an environment permissive for invasion by keratinocytes, which are in various stages of differentiation having downregulated GLI2. Thus, upregulated GLI2 expression is sufficient to induce a number of the acquired characteristics of tumor cells; however, the stroma, in a tissue-specific manner, determines whether certain GLI2 oncogenic traits are expressed.Oncogene (2009) 28, 625–637; doi:10.1038/onc.2008.421; published online 17 November 2008 [ABSTRACT FROM AUTHOR]