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THE REGULATORY T
CELLS (TREGS
Eman youssif
F O R M E R L Y K N O W N A S S U P P R E S S O R T C E L L S , A R E A
S U B P O P U L A T I O N O F T C E L L S W H I C H M O D U L A T E T H E
I M M U N E S Y S T E M , M A I N T A I N T O L E R A N C E T O S E L F -
A N T I G E N S , A N D A B R O G A T E A U T O I M M U N E D I S E A S E .
M O U S E M O D E L S H AV E S U G G E S T E D T H A T
M O D U L A T I O N O F T R E G S C A N T R E A T A U T O I M M U N E
D I S E A S E A N D C A N C E R , A N D F A C I L I T A T E O R G A N
T R A N S P L A N T A T I O N .
T R E G U L A T O R Y C E L L S A R E A C O M P O N E N T O F T H E
I M M U N E S Y S T E M T H A T S U P P R E S S I M M U N E
R E S P O N S E S O F O T H E R C E L L S . T H I S I S A N
I M P O R T A N T " S E L F - C H E C K " B U I L T I N T O T H E I M M U N E
S Y S T E M T O P R E V E N T E X C E S S I V E R E A C T I O N S .
R E G U L A T O R Y T C E L L S C O M E I N M A N Y F O R M S W I T H
T H E M O S T W E L L - U N D E R S T O O D B E I N G T H O S E T H A T
E X P R E S S C D 4 , C D 2 5 , A N D F O X P 3 ( C D 4 + C D 2 5 +
R E G U L A T O R Y T C E L L S , O R " T R E G S " ) . [ 1 ] T H E S E C E L L S
A R E I N V O L V E D I N S H U T T I N G D O W N I M M U N E
R E S P O N S E S A F T E R T H E Y H AV E S U C C E S S F U L L Y
E L I M I N A T E D I N VA D I N G O R G A N I S M S , A N D A L S O I N
P R E V E N T I N G A U T O I M M U N I T Y
C D 4 + F O X P 3 + R E G U L A T O R Y T C E L L S H AV E B E E N
C A L L E D " N A T U R A L L Y - O C C U R R I N G " R E G U L A T O R Y T
C E L L S T O D I S T I N G U I S H T H E M F R O M " S U P P R E S S O R " T
C E L L P O P U L A T I O N S T H A T A R E G E N E R A T E D I N V I T R O .
A D D I T I O N A L S U P P R E S S O R T C E L L P O P U L A T I O N S
I N C L U D E T R 1 , T H 3 , C D 8 + C D 2 8 - , A N D Q A - 1 R E S T R I C T E D
T C E L L S . T H E C O N T R I B U T I O N O F T H E S E P O P U L A T I O N S
T O S E L F - T O L E R A N C E A N D I M M U N E H O M E O S T A S I S I S
L E S S W E L L D E F I N E D. F O X P 3 C A N B E U S E D A S A G O O D
M A R K E R F O R M O U S E C D 4 + C D 2 5 + T C E L L S , A L T H O U G H
R E C E N T S T U D I E S H AV E A L S O S H O W N E V I D E N C E F O R
F O X P 3 E X P R E S S I O N I N C D 4 + C D 2 5 - T C E L L S . I N
H U M A N S , F O X P 3 I S A L S O E X P R E S S E D B Y R E C E N T L Y
A C T I VA T E D C O N V E N T I O N A L T - C E L L S A N D T H U S D O E S
N O T S P E C I F I C A L L Y I D E N T I F Y H U M A N T - R E G
. [ C I T A T I O N N E E D E D ] A N A D D I T I O N A L R E G U L A T O R Y T
C E L L S U B S E T , I N D U C E D R E G U L A T O R Y T C E L L S , A R E
A L S O N E E D E D F O R T O L E R A N C E A N D S U P P R E S S I O N
A L L T C E L L S C O M E F R O M P R O G E N I T O R C E L L S F R O M T H E
B O N E M A R R O W , W H I C H B E C O M E C O M M I T T E D T O T H E I R
L I N E A G E I N T H E T H Y M U S . A L L T C E L L S B E G I N A S C D 4 - C D 8 -
T C R - C E L L S A T T H E D N ( D O U B L E - N E G A T I V E ) S T A G E , W H E R E
A N I N D I V I D U A L C E L L W I L L R E A R R A N G E I T S T C E L L R E C E P T O R
G E N E S T O F O R M A U N I Q U E , F U N C T I O N A L M O L E C U L E , W H I C H
T H E Y , I N T U R N , T E S T A G A I N S T C E L L S I N T H E T H Y M I C
C O R T E X F O R A M I N I M A L L E V E L O F I N T E R A C T I O N W I T H S E L F -
M H C . I F T H E Y R E C E I V E T H E S E S I G N A L S , T H E Y P R O L I F E R A T E
A N D E X P R E S S B O T H C D 4 A N D C D 8 , B E C O M I N G D O U B L E -
P O S I T I V E C E L L S . T H E S E L E C T I O N O F T R E G S O C C U R S O N
R A D I O - R E S I S T A N T H A E M O P O I E T I C A L L Y - D E R I V E D M H C C L A S S
I I - E X P R E S S I N G C E L L S I N T H E M E D U L L A O R H A S S A L ’ S
C O R P U S C L E S I N T H E T H Y M U S . A T T H E D P ( D O U B L E - P O S I T I V E )
S T A G E , T H E Y A R E S E L E C T E D B Y T H E I R I N T E R A C T I O N W I T H
T H E C E L L S W I T H I N T H E T H Y M U S , B E G I N T H E T R A N S C R I P T I O N
O F F O X P 3 , A N D B E C O M E T R E G C E L L S , A L T H O U G H T H E Y M A Y
N O T B E G I N T O E X P R E S S F O X P 3 U N T I L T H E S I N G L E - P O S I T I V E
S T A G E , A T W H I C H P O I N T T H E Y A R E F U N C T I O N A L T R E G S .
T R E G D O N O T H A V E T H E L I M I T E D T C R E X P R E S S I O N O F N K T
O R Γ Δ T C E L L S ; T R E G H A V E A L A R G E R T C R D I V E R S I T Y T H A N
E F F E C T O R T C E L L S , B I A S E D T O W A R D S S E L F - P E P T I D E S .

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The regulatory t cells (tregs

  • 1. THE REGULATORY T CELLS (TREGS Eman youssif
  • 2. F O R M E R L Y K N O W N A S S U P P R E S S O R T C E L L S , A R E A S U B P O P U L A T I O N O F T C E L L S W H I C H M O D U L A T E T H E I M M U N E S Y S T E M , M A I N T A I N T O L E R A N C E T O S E L F - A N T I G E N S , A N D A B R O G A T E A U T O I M M U N E D I S E A S E . M O U S E M O D E L S H AV E S U G G E S T E D T H A T M O D U L A T I O N O F T R E G S C A N T R E A T A U T O I M M U N E D I S E A S E A N D C A N C E R , A N D F A C I L I T A T E O R G A N T R A N S P L A N T A T I O N .
  • 3. T R E G U L A T O R Y C E L L S A R E A C O M P O N E N T O F T H E I M M U N E S Y S T E M T H A T S U P P R E S S I M M U N E R E S P O N S E S O F O T H E R C E L L S . T H I S I S A N I M P O R T A N T " S E L F - C H E C K " B U I L T I N T O T H E I M M U N E S Y S T E M T O P R E V E N T E X C E S S I V E R E A C T I O N S . R E G U L A T O R Y T C E L L S C O M E I N M A N Y F O R M S W I T H T H E M O S T W E L L - U N D E R S T O O D B E I N G T H O S E T H A T E X P R E S S C D 4 , C D 2 5 , A N D F O X P 3 ( C D 4 + C D 2 5 + R E G U L A T O R Y T C E L L S , O R " T R E G S " ) . [ 1 ] T H E S E C E L L S A R E I N V O L V E D I N S H U T T I N G D O W N I M M U N E R E S P O N S E S A F T E R T H E Y H AV E S U C C E S S F U L L Y E L I M I N A T E D I N VA D I N G O R G A N I S M S , A N D A L S O I N P R E V E N T I N G A U T O I M M U N I T Y
  • 4. C D 4 + F O X P 3 + R E G U L A T O R Y T C E L L S H AV E B E E N C A L L E D " N A T U R A L L Y - O C C U R R I N G " R E G U L A T O R Y T C E L L S T O D I S T I N G U I S H T H E M F R O M " S U P P R E S S O R " T C E L L P O P U L A T I O N S T H A T A R E G E N E R A T E D I N V I T R O . A D D I T I O N A L S U P P R E S S O R T C E L L P O P U L A T I O N S I N C L U D E T R 1 , T H 3 , C D 8 + C D 2 8 - , A N D Q A - 1 R E S T R I C T E D T C E L L S . T H E C O N T R I B U T I O N O F T H E S E P O P U L A T I O N S T O S E L F - T O L E R A N C E A N D I M M U N E H O M E O S T A S I S I S L E S S W E L L D E F I N E D. F O X P 3 C A N B E U S E D A S A G O O D M A R K E R F O R M O U S E C D 4 + C D 2 5 + T C E L L S , A L T H O U G H R E C E N T S T U D I E S H AV E A L S O S H O W N E V I D E N C E F O R F O X P 3 E X P R E S S I O N I N C D 4 + C D 2 5 - T C E L L S . I N H U M A N S , F O X P 3 I S A L S O E X P R E S S E D B Y R E C E N T L Y A C T I VA T E D C O N V E N T I O N A L T - C E L L S A N D T H U S D O E S N O T S P E C I F I C A L L Y I D E N T I F Y H U M A N T - R E G . [ C I T A T I O N N E E D E D ] A N A D D I T I O N A L R E G U L A T O R Y T C E L L S U B S E T , I N D U C E D R E G U L A T O R Y T C E L L S , A R E A L S O N E E D E D F O R T O L E R A N C E A N D S U P P R E S S I O N
  • 5. A L L T C E L L S C O M E F R O M P R O G E N I T O R C E L L S F R O M T H E B O N E M A R R O W , W H I C H B E C O M E C O M M I T T E D T O T H E I R L I N E A G E I N T H E T H Y M U S . A L L T C E L L S B E G I N A S C D 4 - C D 8 - T C R - C E L L S A T T H E D N ( D O U B L E - N E G A T I V E ) S T A G E , W H E R E A N I N D I V I D U A L C E L L W I L L R E A R R A N G E I T S T C E L L R E C E P T O R G E N E S T O F O R M A U N I Q U E , F U N C T I O N A L M O L E C U L E , W H I C H T H E Y , I N T U R N , T E S T A G A I N S T C E L L S I N T H E T H Y M I C C O R T E X F O R A M I N I M A L L E V E L O F I N T E R A C T I O N W I T H S E L F - M H C . I F T H E Y R E C E I V E T H E S E S I G N A L S , T H E Y P R O L I F E R A T E A N D E X P R E S S B O T H C D 4 A N D C D 8 , B E C O M I N G D O U B L E - P O S I T I V E C E L L S . T H E S E L E C T I O N O F T R E G S O C C U R S O N R A D I O - R E S I S T A N T H A E M O P O I E T I C A L L Y - D E R I V E D M H C C L A S S I I - E X P R E S S I N G C E L L S I N T H E M E D U L L A O R H A S S A L ’ S C O R P U S C L E S I N T H E T H Y M U S . A T T H E D P ( D O U B L E - P O S I T I V E ) S T A G E , T H E Y A R E S E L E C T E D B Y T H E I R I N T E R A C T I O N W I T H T H E C E L L S W I T H I N T H E T H Y M U S , B E G I N T H E T R A N S C R I P T I O N O F F O X P 3 , A N D B E C O M E T R E G C E L L S , A L T H O U G H T H E Y M A Y N O T B E G I N T O E X P R E S S F O X P 3 U N T I L T H E S I N G L E - P O S I T I V E S T A G E , A T W H I C H P O I N T T H E Y A R E F U N C T I O N A L T R E G S . T R E G D O N O T H A V E T H E L I M I T E D T C R E X P R E S S I O N O F N K T O R Γ Δ T C E L L S ; T R E G H A V E A L A R G E R T C R D I V E R S I T Y T H A N E F F E C T O R T C E L L S , B I A S E D T O W A R D S S E L F - P E P T I D E S .