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 exotoxins A and C.
Cultivation of peripheral blood mononuclear cells (PBMC) in the presence of streptococcal pyrogenic exotoxins (SPE) A and C resulted in a significant induction of sister chromatid exchange (SCE)-inducing DNA lesions. Concomitantly, the expression of interleukin-2 receptor alpha chain (IL-2R alpha chain), transferrin receptor (TfR), and major histocompatibility complex class II molecule HLA-DR on the surface of phytohemagglutinin-activated T cells from whole blood culture cells (WBCC) significantly decreased within 72 h, that is at least two cell cycles, whereas unstimulated T cells from WBCC did not express these markers but had lost their CD3 molecules, an effect reported to precede apoptosis as part of a T cell inactivation pathway. However, no apoptotic cells were observed within a cultivation period of 120 h. We observed clearcut differences in the responses towards SPE A in WBCC and isolated lymphocytes, since SPE A-treated lymphocytes showed an increase in the [3H]thymidine incorporation and did express IL-2R alpha chain and TfR on their cell surface. Regardless of the precise underlying mechanism, T cells from WBCC seem to be in a state of functional incompetence. The data presented here are the first to provide strong evidence that streptococcal toxins produce SCE-inducing DNA lesions in PBMC, an effect that might contribute to the process of immune cell lethality in streptococcal toxic shock-like syndrome and could be of pivotal importance in the pathogenesis of severe streptococcal disease.
Büssing
A
A
Institute of Medical Immunology, Technical University (RWTH) Aachen, Germany.
Klotz
M
M
Suzart
K
K
Efferth
T
T
Gerlach
D
D
Schnitzler
N
N
Osieka
R
R
Schweizer
K
K
Kaufhold
A
A
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001426:Bacterial Proteins; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D005098:Exotoxins / Q000633:toxicity*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D008565:Membrane Proteins; D011990:Receptors, Transferrin / Q000032:analysis; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013297:Streptococcus pyogenes / Q000472:pathogenicity*
D015703:Antigens, CD; D001426:Bacterial Proteins; D005098:Exotoxins; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C117980:SpeA protein, Streptococcus pyogenes; C027951:erythrogenic toxin