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Chapter 5 : Superantigens from Gram-Negative Bacteria and the Diseases That They Cause
Authors:
Takehiko Uchiyama1,
Tohru Miyoshi-Akiyama2,
Hidehiro Ueshiba3
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Affiliations:
1: Department of Human Science, Tokiwa University, Mito, 310-8585, Japan;
2: Department of Infectious Disease, International Medical Center of Japan, Tokyo, 162-8655, Japan;
3: Institute of Laboratory Animals, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan
Content Type: Monograph
Publication Year:
2007
Category: Bacterial Pathogenesis; Immunology
Book DOI:
10.1128/9781555815844
Chapter DOI:
10.1128/9781555815844.ch5
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Abstract:
Yersinia pseudotuberculosis-derived mitogens (YPMs) a, b, and c, have been identified as superantigen (SAg) from gram-negative bacteria. The T-cell activation by SAgs triggers the pathological changes that are based on multiple organ failure, seen in several infectious diseases, such as acute and systemic Y. pseudotuberculosis infection, toxic shock syndrome (TSS) in children and adults, and TSS in neonates, neonatal TSS-like exanthematous disease (NTED). This chapter reviews progress in research on YPMs and the diseases caused by them. It also discusses research findings in TSS and NTED, because these findings provide clues to the pathogenic mechanism of systemic Y. pseudotuberculosis infection. Genes encoding SAgs are frequently carried within mobile genetic elements, especially bacteriophages, and several features of YPMs strongly suggest involvement of mobile genetic elements in carrying the SAg genes. First, YPM genes have not been present in all Y. pseudotuberculosis strains examined. Second, their guanine and cytosine (GC) content is significantly lower (34.6 to 35.3%) than in the genomic core (46.5%). The authors reproduced the response patterns seen in patients with TSS and systemic Y. pseudotuberculosis infection in mouse experiments. They hypothesize that the biased expansion is based on different binding affinities of TCR Vβ-elements for the complex of SAg/MHC class II molecules. Patients with TSS and systemic Y. pseudotuberculosis infection exhibit overlapping clinical manifestations. An NTED patient with exceptionally severe clinical manifestations was found to have an adult-type massive, protracted expansion of Vβ-2+ T cells.
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
Figures
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause
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Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05fig01
Figure 1.
Deduced amino acid sequences of the mature types of YPMa, YPMb, and YPMc. Amino acids are represented by the single-letter code. Numbering of the amino acids starts at the amino terminus of the mature types of YPMa, YPMb, and YPMc. Identical amino acids compared with YPMa are indicated with dashes (-). Dots (•) indicate deletions. YPMa, from references
13
and
21
; YPMb, from reference
25
; YPMc, from reference
5
.
10.1128/9781555815844/f0078-01_thmb.gif
10.1128/9781555815844/f0078-01.gif
Figure 1.
Deduced amino acid sequences of the mature types of YPMa, YPMb, and YPMc. Amino acids are represented by the single-letter code. Numbering of the amino acids starts at the amino terminus of the mature types of YPMa, YPMb, and YPMc. Identical amino acids compared with YPMa are indicated with dashes (-). Dots (•) indicate deletions. YPMa, from references 13 and 21 ; YPMb, from reference 25 ; YPMc, from reference 5 .
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05fig02
Figure 2.
Different patterns of expansion of Vβ2+ T cells in adult TSS patients and neonatal NTED patients. Two adult TSS patients (A) (
,
) and four neonatal NTED patients (B) (
,
,
,
) were monitored for the percentage of Vβ2+ CD4+ T cells among PBMs. Data are expressed as functions of days after hospital admission (A) and the age of the patients (B). Symbols:
in panel A, means ± standard deviation in seven healthy individuals;
in panel B, one neonate at age 39 days;
in panel B, methicillin-resistant S. aureus (MRSA)-free neonates at age 5 days. The percentages of Vβ2+CD8+ T cells in adult TSS patients and neonatal NTED patients were similar to the percentages of Vβ2+CD4+ T cells. Data in panels A and B are from references
18
and
29
, respectively.
,
) and four neonatal NTED patients (B) (
,
,
,
) were monitored for the percentage of Vβ2+ CD4+ T cells among PBMs. Data are expressed as functions of days after hospital admission (A) and the age of the patients (B). Symbols:
in panel A, means ± standard deviation in seven healthy individuals;
in panel B, one neonate at age 39 days;
in panel B, methicillin-resistant S. aureus (MRSA)-free neonates at age 5 days. The percentages of Vβ2+CD8+ T cells in adult TSS patients and neonatal NTED patients were similar to the percentages of Vβ2+CD4+ T cells. Data in panels A and B are from references
18
and
29
, respectively.10.1128/9781555815844/f0082-01_thmb.gif
10.1128/9781555815844/f0082-01.gif
Figure 2.
Different patterns of expansion of Vβ2+ T cells in adult TSS patients and neonatal NTED patients. Two adult TSS patients (A) (
,
) and four neonatal NTED patients (B) (
,
,
,
) were monitored for the percentage of Vβ2+ CD4+ T cells among PBMs. Data are expressed as functions of days after hospital admission (A) and the age of the patients (B). Symbols:
in panel A, means ± standard deviation in seven healthy individuals;
in panel B, one neonate at age 39 days;
in panel B, methicillin-resistant S. aureus (MRSA)-free neonates at age 5 days. The percentages of Vβ2+CD8+ T cells in adult TSS patients and neonatal NTED patients were similar to the percentages of Vβ2+CD4+ T cells. Data in panels A and B are from references
18
and
29
, respectively.
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05fig03
Figure 3.
Expansion of YPMa-reactive and SEA-reactive T-cell fractions in mice implanted with osmotic pumps filled with YPMa or SEA. (A) C57Bl/6 mice implanted with an osmotic pump filled with 300 μg of YPMa were monitored for responses by Vβ7CD4+ (
), Vβ7CD8+ (
), Vβ8+CD4+ (
), and Vβ8+CD8+ (
) splenic T cells. (B) C57BL/6 mice implanted with an osmotic pump filled with 10 μg of SEA were monitored individually for responses by Vβ3CD4+ (
), Vβ3CD8+ (
), Vβ11+CD4+ (
), and Vβ11 +CD8+ splenic T cells (
). Data are shown as percentages of the YPMa-reactive or SEA-reactive T cells. Data in panels A and B are from reference
6
.
), Vβ7CD8+ (
), Vβ8+CD4+ (
), and Vβ8+CD8+ (
) splenic T cells. (B) C57BL/6 mice implanted with an osmotic pump filled with 10 μg of SEA were monitored individually for responses by Vβ3CD4+ (
), Vβ3CD8+ (
), Vβ11+CD4+ (
), and Vβ11 +CD8+ splenic T cells (
). Data are shown as percentages of the YPMa-reactive or SEA-reactive T cells. Data in panels A and B are from reference
6
.10.1128/9781555815844/f0083-01_thmb.gif
10.1128/9781555815844/f0083-01.gif
Figure 3.
Expansion of YPMa-reactive and SEA-reactive T-cell fractions in mice implanted with osmotic pumps filled with YPMa or SEA. (A) C57Bl/6 mice implanted with an osmotic pump filled with 300 μg of YPMa were monitored for responses by Vβ7CD4+ (
), Vβ7CD8+ (
), Vβ8+CD4+ (
), and Vβ8+CD8+ (
) splenic T cells. (B) C57BL/6 mice implanted with an osmotic pump filled with 10 μg of SEA were monitored individually for responses by Vβ3CD4+ (
), Vβ3CD8+ (
), Vβ11+CD4+ (
), and Vβ11 +CD8+ splenic T cells (
). Data are shown as percentages of the YPMa-reactive or SEA-reactive T cells. Data in panels A and B are from reference
6
.
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05fig04
Figure 4.
Skin rashes observed in patients with acute and systemic Y. pseudotuberculo-sis infection. The incidence of skin rashes, including primary and secondary exan-thems, desquamation, and erythema nodosum in patients in the mass outbreak of systemic Y. pseudotuberculosis infection that occurred in Japan in 1986 (
10
) is shown. Data are from reference
10
.
10.1128/9781555815844/f0085-01_thmb.gif
10.1128/9781555815844/f0085-01.gif
Figure 4.
Skin rashes observed in patients with acute and systemic Y. pseudotuberculo-sis infection. The incidence of skin rashes, including primary and secondary exan-thems, desquamation, and erythema nodosum in patients in the mass outbreak of systemic Y. pseudotuberculosis infection that occurred in Japan in 1986 ( 10 ) is shown. Data are from reference 10 .
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05fig05
Figure 5.
TCR Vβ expression in acute and convalescent patients with acute, generalized Y. pseudotuberculosis infection. T cells of patients with acute, generalized Y. pseudotuberculosis infection were examined for TCR Vβ expression by RT-PCR. Acute, within 20 days of the disease onset; conv (convalescent), later than 120 days after the disease onset. The original figure is provided by J. Abe in reference
2
.
10.1128/9781555815844/f0086-01_thmb.gif
10.1128/9781555815844/f0086-01.gif
Figure 5.
TCR Vβ expression in acute and convalescent patients with acute, generalized Y. pseudotuberculosis infection. T cells of patients with acute, generalized Y. pseudotuberculosis infection were examined for TCR Vβ expression by RT-PCR. Acute, within 20 days of the disease onset; conv (convalescent), later than 120 days after the disease onset. The original figure is provided by J. Abe in reference 2 .
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
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Tables
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause
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Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05tab01
Table 1.
TCR Vβ repertoires of YPMa-reactive T cells and their relative YPMa reactivity
Table 1.
TCR Vβ repertoires of YPMa-reactive T cells and their relative YPMa reactivity
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5
/content/10.1128/9781555815844.ch05.ch05tab02
Table 2.
Examination for YPM production by 101 Y. pseudotuberculosis strains
a
Table 2.
Examination for YPM production by 101 Y. pseudotuberculosis strains a
Citation:
Uchiyama T, Miyoshi-Akiyama T, Ueshiba H.
2007.
Superantigens from Gram-Negative Bacteria and the Diseases That They Cause,
p 77-89.
In
Kotb M, Fraser J (ed),
Superantigens.
ASM Press, Washington, DC.
doi: 10.1128/9781555815844.ch5