Diversity of physiological cell reactivity to heat shock protein 60 in different mouse strains.
Heat shock proteins (Hsp) are families of highly conserved molecules and immunodominant antigens in some infections and in autoimmune diseases. Some reports suggest that different regions of the Hsp60 molecule induce distinct immune responses. However, there are no reports comparing physiological T-cell reactivity to Hsp60 in mice. In this study, we have analyzed T-cell proliferation and cytokine production induced by Hsp60, under physiological conditions, in three mouse strains bearing distinct major histocompatibility complex (MHC) backgrounds. Proliferative response predominantly was found in C57BL/6 mice, mostly induced by N-terminal and intermediate Hsp60 peptides (P < 0.0001). Interferon-gamma (IFNgamma) production was broadly induced by different regions of Hsp60 in all three mouse strains, although response was focused in different peptide groups in each strain. We did not observe an exclusive Th1 or Th2 cytokine profile induced by any particular region of Hsp60. However, we identified a strain hierarchy in IL-10 production induced by Hsp60 peptides from different regions, mostly detected in C3H/HePas, and in BALB/c, but not in C57BL/6 mice. In contrast, IL-4 production only was induced by the intermediate and C-terminal region peptides in both C3H/HePas and BALB/c mice. Our data give original information on physiological cellular reactivity to Hsp60. We also have identified peptides with the capacity to induce the production of anti-inflammatory cytokines, bringing perspectives for their use in immunotherapy of chronic inflammatory diseases and allograft rejection.
Luna
Ernesto
E
Heart Institute (InCor) University of Săo Paulo Medical School, Săo Paulo, SP, CEP 05403-000, Brazil.
Postol
Edilberto
E
Caldas
Cristina
C
Mundel
Luiz R
LR
Porto
Georgia
G
Iwai
Leo K
LK
Ho
Paulo Lee
PL
Kalil
Jorge
J
Coelho
Verônica
V
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens; D049109:Cell Proliferation / Q000187:drug effects; D018834:Chaperonin 60 / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D000941:Antigens; D018834:Chaperonin 60; D010455:Peptides; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
J Immunol. 2000 Jan 15;164(2):558-61
10623794
Circulation. 2002 Sep 24;106(13):1708-15
12270867
J Immunol. 2000 Dec 15;165(12):7270-7
11120861
Lancet. 2001 Nov 24;358(9295):1749-53
11734230
Diabetologia. 2002 Oct;45(10):1468-74
12378391
J Immunol. 2003 Mar 1;170(5):2340-8
12594256
Arthritis Rheum. 2003 Jul;48(7):2001-10
12847694
FASEB J. 2003 Aug;17(11):1567-9
12824285
Eur J Immunol. 2004 Jul;34(7):2041-51
15214052
Nature. 1988 Jan 14;331(6152):171-3
2448638
J Cell Physiol. 1989 Feb;138(2):257-66
2918030
Annu Rev Genet. 1988;22:631-77
2853609
Proc Natl Acad Sci U S A. 1990 Feb;87(4):1576-80
2406723
J Exp Med. 1990 Mar 1;171(3):831-41
1689764
Immunol Today. 1990 Apr;11(4):129-36
2187470
J Immunol Methods. 1990 Sep 14;132(2):191-5
2170533
Immunol Today. 1993 Mar;14(3):115-8
8466626
Lancet. 1994 Mar 19;343(8899):704-6
7907681
Annu Rev Immunol. 1994;12:991-1045
8011301
Transplantation. 1995 Feb 27;59(4):598-604
7878764
J Autoimmun. 1996 Apr;9(2):159-66
8738959
J Exp Med. 1997 Apr 7;185(7):1307-16
9104817
Diabetes. 1997 May;46(5):758-64
9133541
J Clin Invest. 1997 Jul 15;100(2):459-63
9218524
Methods Enzymol. 1997;289:44-67
9353717
Clin Exp Immunol. 1999 Feb;115(2):260-7
9933451
J Autoimmun. 1999 Mar;12(2):121-9
10047432
J Immunol. 1999 Mar 15;162(6):3212-9
10092772
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5159-63
10220435
J Immunol. 2005 Feb 1;174(3):1298-305
15661886
J Immunol. 2005 Mar 15;174(6):3227-36
15749853
Nat Rev Immunol. 2005 Apr;5(4):318-30
15803151
Contrib Nephrol. 2005;148:122-34
15912031
Lancet. 2005 Jul 2-8;366(9479):50-6
15993233
Int Rev Immunol. 2005 May-Aug;24(3-4):181-97
16036373
J Immunol. 2005 Sep 15;175(6):3594-602
16148103
Hum Immunol. 2006 Jun;67(6):446-53
16728268
Clin Exp Immunol. 2006 Oct;146(1):66-75
16968400
Adv Exp Med Biol. 2003;528:173-80
12918685
J Immunol. 2003 Oct 1;171(7):3533-41
14500649
Inflamm Res. 2003 Nov;52(11):443-51
14652678
J Immunol. 2004 Mar 1;172(5):2795-802
14978079
Biochem Biophys Res Commun. 2004 May 14;317(4):1149-54
15094389
Mol Immunol. 2004 May;41(1):29-44
15140573
Isr Med Assoc J. 2004 May;6(5):260-1
15151361
Clin Exp Immunol. 2004 Jul;137(1):201-8
15196263
Int Immunol. 2000 Jul;12(7):1041-50
10882416