Induced Sézary syndrome PBMCs poorly express immune response genes up-regulated in stimulated memory T cells.
BACKGROUND
Dysfunctions in memory T cells contribute to various inflammatory autoimmune diseases and neoplasms. We hypothesize that investigating the differences of genetic profiles between resting and activated naïve and memory T cells may provide insight into the characterization of abnormal memory T cells in diseases, such as Sézary syndrome (SS), a neoplasm composed of CD4(+) CD45RO(+) cells.


OBJECTIVE
We determined genes distinctively expressed between resting and activated naive and memory cells. Levels of up-regulated genes in resting and activated memory cells were measured in SS PBMCs, which were largely comprised of CD4(+) CD45RO(+) cells, to quantitatively assess how different Sézary cells were from memory cells.


METHODS
We compared gene expression profiles using high-density oligo-microarrays between resting and activated naïve and memory CD4(+) T cells. Differentially expressed genes were confirmed by qRT-PCR and immunoblotting. Levels of genes up-regulated in activated and resting memory T cells were determined in SS PBMCs by qRT-PCR.


RESULTS
Activated memory cells expressed greater numbers of immune-mediated genes involved in effector function compared to naïve cells in our microarray analysis and qRT-PCR. Nine out of 14 genes with enhanced levels in activated memory cells had reduced levels in SS PBMCs (p<0.05).


CONCLUSIONS
Activation of memory and naïve CD4(+) T cells revealed a diverging gap in gene expression between these subsets, with memory cells expressing immune-related genes important for effector function. Many of these genes were markedly depressed in SS patients, implying Sézary cells are markedly impaired in mounting immune responses compared to memory cells.
Chong
Benjamin F
BF
Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA.
Dantzer
Patrick
P
Germeroth
Thomas
T
Hafner
Mikehl
M
Wilson
Adam J
AJ
Xiao
Guanghua
G
Wong
Henry K
HK
D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012751:Sezary Syndrome / Q000235:genetics* / Q000276:immunology; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
D017493:Leukocyte Common Antigens
J Immunol. 1995 Feb 1;154(3):1491-8
7822812
Curr Dir Autoimmun. 2008;10:119-40
18460883
J Immunol. 2000 Jun 15;164(12):6621-32
10843722
J Invest Dermatol. 1994 Jul;103(1):29-33
8027577
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2976-81
10077622
J Clin Immunol. 1997 Jul;17(4):265-71
9258765
Science. 1995 Oct 20;270(5235):467-70
7569999
J Invest Dermatol. 2009 Dec;129(12):2875-85
19626037
J Immunol. 1993 Mar 1;150(5):2081-9
7679701
J Biol Chem. 1998 Aug 7;273(32):20551-5
9685412
Leukemia. 2008 Feb;22(2):393-9
18033314
Clin Exp Immunol. 2004 Dec;138(3):491-8
15544627
Blood. 2000 Jul 15;96(2):685-90
10887135
Curr Opin Immunol. 1994 Jun;6(3):431-7
7917111
J Exp Med. 1991 Jan 1;173(1):25-36
1898663
Immunology. 1992 May;76(1):103-9
1352764
Eur J Immunol. 2002 May;32(5):1264-73
11981813
Rinsho Byori. 2007 Jan;55(1):51-8
17319491
J Immunol. 2000 Dec 15;165(12):6677-81
11120783
Cytokine. 1999 Apr;11(4):257-66
10328864
J Immunol. 1998 Jul 15;161(2):674-83
9670942
J Immunol. 2001 Jun 15;166(12):7335-44
11390484
J Immunol. 1995 Apr 1;154(7):3078-87
7897199
J Immunol. 1999 Aug 1;163(3):1682-9
10415075
Science. 1997 Jun 27;276(5321):2057-62
9197272
Curr Dir Autoimmun. 2008;10:65-75
18460881
Genome Biol. 2003;4(10):R70
14519205
J Mol Med (Berl). 2005 Mar;83(3):170-9
15776286
J Immunol. 1999 Jan 1;162(1):186-94
9886385
Int Immunol. 1993 Nov;5(11):1483-7
7505109
Methods. 2001 Dec;25(4):402-8
11846609
Cytokine. 1992 Nov;4(6):461-9
1292630
J Immunol. 1992 Oct 1;149(7):2300-6
1388189
Curr Dir Autoimmun. 2008;10:313-32
18460893
Blood. 2007 Jul 15;110(2):479-84
17339420
J Immunol. 2000 Jan 1;164(1):265-72
10605020
J Invest Dermatol. 1992 Jul;99(1):90-4
1607682
J Immunol. 1994 Mar 15;152(6):2675-85
7908301
Arthritis Rheum. 2007 Sep;56(9):2936-46
17763419
BMC Cancer. 2008 Feb 04;8:41
18248671
Leukemia. 2008 Dec;22(12):2230-9
18769452
Clin Cancer Res. 2008 Feb 1;14(3):646-53
18245523
Science. 1998 Jan 16;279(5349):381-4
9430588