Nonspecific T-lymphocyte mitogenesis by pyrogenic exotoxins from group A streptococci and Staphylococcus aureus

Schlievert, P M; Schoettle, D J; Watson, Dennis W.

doi:10.1128/iai.25.3.1075-1077.1979

Cited by 37 publications

(23 citation statements)

References 14 publications

(9 reference statements)

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“…Furthermore, PE type C has profound effects on the host immune system, including nonspecific stimulation of T lymphocytes (19), suppression of immunoglobulin M synthesis (19), and enhancement of acquired hypersensitivity to induce a skin rash. These properties are shared by all PEs thus far described (2,4,5,8,12,17,18).…”

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confidence: 89%

Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C

Schlievert¹

1982

Infect Immun

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168

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Staphylococcal pyrogenic exotoxin (PE) type C enhanced the susceptibility of rabbits to lethal shock by endotoxin by as much as 50,000-fold. A graph of log PE type C dose used for pretreatment versus log 50% lethal dose of endotoxin gave a straight line with a slope of approximately-1. Rabbits that received PE type C alone showed fevers only, but those given both PE type C and endotoxin showed initial fever followed by hypothermia, labored breathing, diarrhea, evidence of vascular collapse, and finally death. When a PE type C dose of 3 ,ug/kg was used, pretreatment of the animals with PE for 2 h before giving the endotoxin was required to obtain maximal susceptibility. However, when 15 ,ug of PE type C per kg was utilized, the endotoxin could be given before, concurrently, or after PE type C. The capacity of PE type C to prepare rabbits for enhanced susceptibility to endotoxin was lost after 24 to 48 h. Animals could be protected from enhanced susceptibility to endotoxin by prior immunization with either PE type C or endotoxin. However, 30% of the rabbits which were immunized with PE type C failed to develop immunity, and after three injections of PE type C, these animals developed gram-negative bacteremia and succumbed. In addition, rabbits with diarrhea initially, possibly caused by Pasteurella infection, died less than 24 h after a single injection of PE type C.

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confidence: 89%

Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C

Schlievert¹

1982

Infect Immun

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168

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“…tococcus pyogenes have been shown to be T-cell mitogens, capable of activating T cells which can suppress the immune response (3,9,10,25,26,28). The enterotoxin from Vibrio cholerae can also enhance or suppress the immune response which is dependent on the timing of toxin administration relative to antigen stimulation (13,16).…”

Section: Discussionmentioning

confidence: 99%

Variables which affect suppression of the immune response induced by Pseudomonas aeruginosa exotoxin A

Holt¹,

Misfeldt²

1986

Infect Immun

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Pseudomonas exotoxin A has been shown previously to induce suppression of the murine immune response. In the present study, various parameters were examined which may have an effect on immunosuppression. The addition of 10-4 ng of exotoxin A induced suppression of the immune response to trinitrophenylated Ficoll from days 3 to 10, while 10 ng of toxin exerted no suppressive effect over the same examination periods. When the toxin was administered 1 or 2 days before antigen stimulation, suppression of the response was observed with both 10 and 10-4 ng. Priming splenocytes with toxin either in vivo or in vitro for 1 or 2 days suppressed the response of fresh cultured splenocytes to antigenic stimulation. Heated toxin, photoaffinity-labeled toxin, or preincubation of the toxin with rabbit anti-exotoxin A antiserum eliminated the toxin-induced suppression. These results suggest that Pseudomonas exotoxin A can generate multiple biological effects.Exotoxin A is a protein toxin produced by the gramnegative bacterium Pseudomonas aeruginosa. The toxin has been shown to be directly cytotoxic for a number of mammalian cells primarily through the ADP ribosylation of protein elongation factor 2, thereby inhibiting cellular polypeptide synthesis (18,20,21). We have been studying the effects of exotoxin A on the murine immune response and have found that the toxin can induce suppression in euthymic nul+ mice to thymus-dependent and thymusindependent antigens both in vitro and in vivo (11). The suppression was observed over a toxin range of 1 to 10-6 ng, while 10 and 100 ng had no apparent effect (11). A number of parameters can influence the overall action of immunomodifiers. Tubercle bacilli have been observed to elicit an immunoenhancing effect when administered with the antigen (7) but to induce suppression of the response when given before the antigen (31). A similar effect has also been observed for cholera toxin (13, 16) and Bordetella pertussis vaccine (6). We now report that timing of exotoxin A administration relative to antigenic stimulation can have a dramatic effect on the ability of the toxin to modify the immune response. Given concomitantly with the antigen, 10 ng of exotoxin A is not immunosuppressive. However, this same dose of toxin induced suppression when administered 1 or 2 days before the antigen stimulation. Modification of the toxin by heating, photoaffinity labeling, or preincubation with rabbit anti-exotoxin A antibodies eliminated the capacity of exotoxin A to induce suppression. These studies support the concept that Pseuidomonas exotoxin A is a potent biological response modifier. MATERIALS AND METHODS Mice. NFR/N (H-2q) nul+ mice were derived from brother-and-sister breeding pairs maintained in the animal care facilities at the University of Missouri-Columbia School of Medicine from breeding stock originally obtained from Carl * Corresponding author. t Present address: Veterinary Toxicology and Entomology Research Laboratory, U.S. Department of Agriculture, College Station, TX 77841.Hansen, Nationa...

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“…On the other hand, Schlievert et al (34,35) reported that a pyrogenic exotoxin from S. aureus as well as from Streptococcus pyogenes has mitogenic activity for human T lymphocytes and rabbit splenocytes. No information on the production of pyrogenic toxin(s) by S. aureus L-forms, is available, but the data from this study as a whole suggest only a slight, if any, possibility that pyrogenic exotoxin is involved in our preparations .…”

Section: Discussionmentioning

confidence: 99%

Mitogenic Activity of Cytoplasmic Membranes Isolated from L‐Forms of Staphylococcus aureus

Takada

Hirachi

Hashizume

et al. 1980

Microbiology and Immunology

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Cytoplasmic membranes of L-forms of Staphylococcus aureus exerted a strong mitogenic effect on splenocytes of athymic nude mice as well as normal mice, while a cytoplasmic fraction of the same bacteria did not show definite mitogenicity. The mitogenic principle(s) of the membrane fraction was resistant to treatment with trypsin and was heat stable (at 100 C for 10 min). The active principle(s) in the insoluble residue of the membrane fraction digested with trypsin was not extracted with cold acetone, but could be solubilized by extraction with a cold chloroform-methanol mixture (2 :1, v/v). The mitogenic principle(s) in the extract was fractionated by silicic acid column chromatography. Among five fractions separated by chromatography, fractions eluted with chloroform-methanol mixtures (1:1 and 1:20, v/v) were found to be strongly mitogenic.The cytoplasmic membranes of the L-forms also exerted a definite mitogenic effect on guinea pig splenocytes, but not on the thymocytes.

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Nonspecific T-lymphocyte mitogenesis by pyrogenic exotoxins from group A streptococci and Staphylococcus aureus

Abstract: Group A streptococcal pyrogenic exotoxins types A, B, and C and staphylococcal pyrogenic exotoxin were shown to be potent nonspecific T-lymphocyte mitogens. Adherent cell populations did not significantly affect the nonspecific mitogenicity.

Cited by 37 publications

References 14 publications

Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C

Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C

Variables which affect suppression of the immune response induced by Pseudomonas aeruginosa exotoxin A

Mitogenic Activity of Cytoplasmic Membranes Isolated from L‐Forms of Staphylococcus aureus

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