Mast cell degranulation breaks peripheral tolerance.
Mast cells (MC) have been shown to mediate regulatory T-cell (T(reg))-dependent, peripheral allograft tolerance in both skin and cardiac transplants. Furthermore, T(reg) have been implicated in mitigating IgE-mediated MC degranulation, establishing a dynamic, reciprocal relationship between MC and T(reg) in controlling inflammation. In an allograft tolerance model, it is now shown that intragraft or systemic MC degranulation results in the transient loss of T(reg) suppressor activities with the acute, T-cell dependent rejection of established, tolerant allografts. Upon degranulation, MC mediators can be found in the skin, T(reg) rapidly leave the graft, MC accumulate in the regional lymph node and the T(reg) are impaired in the expression of suppressor molecules. Such a dramatic reversal of T(reg) function and tissue distribution by MC degranulation underscores how allergy may causes the transient breakdown of peripheral tolerance and episodes of acute T-cell inflammation.
de Vries
V C
VC
Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH, USA.
Wasiuk
A
A
Bennett
K A
KA
Benson
M J
MJ
Elgueta
R
R
Waldschmidt
T J
TJ
Noelle
R J
RJ
D000818:Animals; D001483:Base Sequence; D015550:Cell Degranulation; D017931:DNA Primers; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000276:immunology; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D017931:DNA Primers; D018836:Inflammation Mediators
J Immunol. 2003 Dec 1;171(11):5760-8
14634084
Nat Immunol. 2007 Oct;8(10):1095-104
17767162
Nat Med. 2008 May;14(5):536-41
18425129
Int Immunol. 2004 May;16(5):685-95
15096484
J Allergy Clin Immunol. 2008 Sep;122(3):617-24.e6
18672278
J Leukoc Biol. 2000 Oct;68(4):471-8
11037967
J Thorac Cardiovasc Surg. 1998 Mar;115(3):631-6; discussion 636-7
9535451
J Immunol. 1999 Apr 15;162(8):4373-6
10201970
Annu Rev Immunol. 2008;26:705-39
18370925
J Immunol. 2008 Mar 1;180(5):2848-54
18292506
Lancet. 2004 Feb 21;363(9409):608-15
14987885
J Immunol. 1990 Dec 1;145(11):3610-7
2147197
Nature. 1980 Aug 14;286(5774):722-3
6157990
Immunology. 2006 Feb;117(2):196-204
16423055
J Allergy Clin Immunol. 2002 Dec;110(6):934-6
12464962
J Clin Invest. 1996 Mar 15;97(6):1398-408
8617871
Clin Exp Allergy. 2007 Aug;37(8):1127-36
17651141
J Allergy Clin Immunol. 2007 May;119(5):1258-66
17412402
Nature. 2006 Aug 31;442(7106):997-1002
16921386
J Immunol. 2008 Feb 15;180(4):2039-43
18250408
Curr Opin Immunol. 2001 Dec;13(6):701-8
11677093
Mol Immunol. 2002 May;38(12-13):881-5
12009564
J Allergy Clin Immunol. 2008 Jan;121(1):197-202
17904627
Clin Exp Allergy. 2004 Sep;34(9):1364-72
15347368
J Immunol. 2006 Apr 1;176(7):4141-6
16547250
Allergol Int. 2008 Jun;57(2):183
18349593
Nat Rev Immunol. 2008 Jun;8(6):478-86
18483499
Curr Opin Immunol. 2007 Feb;19(1):31-8
17126541
Agents Actions. 1984 Oct;15(3-4):267-72
6084410
Trends Immunol. 2005 Mar;26(3):130-5
15745854
Arch Toxicol. 2004 Nov;78(11):649-54
15205889
J Clin Invest. 2006 Mar;116(3):833-41
16498503
Drug Intell Clin Pharm. 1987 Jan;21(1 Pt 1):22-35
3102198
J Immunol. 2009 Jan 1;182(1):148-53
19109145
J Exp Med. 2005 Dec 5;202(11):1539-47
16314435
Eur J Cardiothorac Surg. 1999 Aug;16(2):150-5
10485412
Blood. 2003 Sep 1;102(5):1920-6
12750162
Arch Dermatol. 1994 May;130(5):584-8
8179340
Immunity. 2008 Nov 14;29(5):771-81
18993084
Nature. 1988 Aug 11;334(6182):499-504
2457169
Transpl Int. 2007 Mar;20(3):256-65
17291219
Immunity. 2005 Mar;22(3):329-41
15780990