SISTER-CHROMATID EXCHANGE INDUCING DNA LESIONS AND DEPRESSION OF ACTIVATION MARKERS ON THE SURFACE OF CULTURED PERIPHERAL-BLOOD MONONUCLEAR-CELLS AFTER THE ADDITION OF STREPTOCOCCAL PYROGENIC EXOTOXIN-A AND EXOTOXINC

Cultivation of peripheral blood mononuclear cells (PBMC) in the presen ce of streptococcal pyrogenic exotoxins (SPE) A and C resulted in a si gnificant induction of sister chromatid exchange (SCE)-inducing DNA le sions. Concomitantly, the expression of interleukin-2 receptor alpha c hain (IL-2R alpha chain), transferrin receptor (TfR), and major histoc ompatibility complex class II molecule HLA-DR on the surface of phytoh emagglutinin - activated T cells from whole blood culture cells (WBCC) significantly decreased within 72 h, that is at least two cell . cycl es, whereas unstimulated T cells from WE CC did not express these mark ers but had lost their CD3 molecules, an effect reported to precede ap optosis as part of a T cell inactivation pathway. However, no apoptoti c cells were observed within a cultivation period of 120 h. We observe d clearcut differences in the responses towards SPE A in WBCC and isol ated lymphocytes, since SPE A-treated lymphocytes showed an increase i n the [H-3]thymidine incorporation and did express IL-2R alpha chain a nd TfR on their cell surface. Regardless of the precise underlying mec hanism, T cells from WBCC seem to be in a state of functional incompet ence. The data presented here are the first to provide strong evidence that streptococcal toxins produce SCE-inducing DNA lesions in PBMC, a n effect that might contribute to the process of immune cell lethality in streptococcal toxic shock-like syndrome and could be of pivotal im portance in the pathogenesis of severe streptococcal disease.