Mucosal but not peripheral FOYP3+ regulatory T cells are highly increased in untreated HIV infection and nonnalize after suppressive HAART

被引:167
作者
Epple, Hans-Joerg
Loddenkemper, Christoph
Kunkel, Desiree
Troeger, Hanno
Maul, Jochen
Moos, Verena
Berg, Erika
Ullrich, Reiner
Schulzke, Joerg-Dieter
Stein, Harald
Duchmann, Rainer
Zeitz, Martin
Schneider, Thomas
机构
[1] Charite Univ Med Berlin, Med Clin 1, D-12200 Berlin, Germany
[2] Charite Univ Med Berlin, Inst Pathol, Reference Ctr Lymph Node Pathol & Haematopathol, D-12200 Berlin, Germany
关键词
D O I
10.1182/blood-2006-04-016923
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent evidence indicates that regulatory T cells (T-regs) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T-regs in HIV infection are available. In this study, we compared the frequency of T-regs in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. T-regs were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal T-regs were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of T-regs was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal T-regs in the CD4(+) T-cell subset was not elevated. The high increase in count and frequency of mucosal T-regs seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of T-regs to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.
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收藏
页码:3072 / 3078
页数:7
相关论文
共 44 条
[1]   Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens [J].
Aandahl, EM ;
Michaëlsson, J ;
Moretto, WJ ;
Hecht, FA ;
Nixon, DF .
JOURNAL OF VIROLOGY, 2004, 78 (05) :2454-2459
[2]   Cutting edge: The prevalence of regulatory T cells lymphoid tissue is correlated with viral load HIV-infected patients [J].
Andersson, J ;
Boasso, A ;
Nilsson, J ;
Zhang, R ;
Shire, NJ ;
Lindback, S ;
Shearer, GM ;
Chougnet, CA .
JOURNAL OF IMMUNOLOGY, 2005, 174 (06) :3143-3147
[3]   FOXP3 mRNA levels are decreased in peripheral blood CD4+ lymphocytes from HIV-positive patients [J].
Apoil, PA ;
Puissant, B ;
Roubinet, F ;
Abbal, M ;
Massip, P ;
Blancher, A .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2005, 39 (04) :381-385
[4]   Replication of M-tropic HIV-1 in activated human intestinal lamina propria lymphocytes is the main reason for increased virus load in the intestinal mucosa [J].
Aziz, S ;
Fackler, OT ;
Meyerhans, A ;
Müller-Lantzsch, N ;
Zeitz, M ;
Schneider, T .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2005, 38 (01) :23-30
[5]   Suppressor T cells in human diseases [J].
Baecher-Allan, C ;
Hafler, DA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (03) :273-276
[6]   Natural regulatory T cells in infectious disease [J].
Belkaid, Y ;
Rouse, BT .
NATURE IMMUNOLOGY, 2005, 6 (04) :353-360
[7]   CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract [J].
Brenchley, JM ;
Schacker, TW ;
Ruff, LE ;
Price, DA ;
Taylor, JH ;
Beilman, GJ ;
Nguyen, PL ;
Khoruts, A ;
Larson, M ;
Haase, AT ;
Douek, DC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (06) :749-759
[8]   Defective dendritic cell function in HIV-infected patients receiving effective highly active antiretroviral therapy:: Neutralization of IL-10 production and depletion of CD4+CD25+ T cells restore high levels of HIV-specific CD4+ T cell responses induced by dendritic cells generated in the presence of IFN-α [J].
Carbonneil, C ;
Donkova-Petrini, V ;
Aouba, A ;
Weiss, L .
JOURNAL OF IMMUNOLOGY, 2004, 172 (12) :7832-7840
[9]   Are regulatory T-cells linked with aging? [J].
Dejaco, Christian ;
Duftner, Christina ;
Schirmer, Michael .
EXPERIMENTAL GERONTOLOGY, 2006, 41 (04) :339-345
[10]   Depletion of regulatory T cells in HIV infection is associated with immune activation [J].
Eggena, MP ;
Barugahare, B ;
Jones, N ;
Okello, M ;
Mutalya, S ;
Kityo, C ;
Mugyenyi, P ;
Cao, HY .
JOURNAL OF IMMUNOLOGY, 2005, 174 (07) :4407-4414