Table 1 Pathogen-induced Tr cells and their role in infection
Pathogen
Tr cell type
Agspecific1
T cell
clones2
Cytokine
secreted
Tr cells suppress3
Manipulation of
Tr cells
Effect on immune response,
immumnopathology and pathogen
burden
Tr1 cell transfer
suppress Th1 response and enhances
bacterial load
28
Defective
Tr1
cells in TLR4-/mice
Tr cell depletion
with anti-GITR
Enhanced
Th1
response,
lung
inflammation and increased bacterial load
67
enhances IFN- secreting CD8 T cells and
reduces viral load
84
CD25 T
depletion
cell
prevents spleen pathology and disease
progression but no effect on viral load
54
CD45RBlow
cell transfer
Tr
prevent colitis in IL-10-/- mice
56
Refs
Bordetella
pertussis
Mouse Tr1
CD4+CD25+
Yes
Yes
IL-10 +/TGF-
Bordetella
pertussis
Mouse Tr1
Yes
Yes
IL-10
Ag-specific Th1 prol
+ IFN- in vitro + in
vivo
Th1 IFN-
Friend virus
Mouse Tr1
IL-10
CD8+ T cell IFN-
Murine leukaemia virus
Mouse Tr1
CD4+CD25+
IL-10
Helicobacter
hepaticus
Mouse
CD45RBlow
Yes
IL-10
Ag-specific IL-10-/CD4+ T cell IFN-
Mycobacteria
tuberculosis
Human Tr1
Yes
IL-10
Allo CD4+ T cells
prol
25,51
Hepatitis C
virus
Epstein Barr
Virus
Onchocerca
volvulus
Hepatitis C
virus
HIV
Human Tr1
Yes
IL-10
PBMC IFN-
46,60
Human Tr1
Yes
IL-10
50
Human
Th3/Tr1
Human
CD8+ Tr
Human
CD8+ Tr
Yes
T cell prol + IFN- to
recall Ag
PBMC prol
Ag-specific PBMC
prol
Vaccinia
virusspecific CD8+ IFN-
49
Yes
Yes
Yes
IL-10 +/TGF-
IL-10
Yes
TGF-
47,48
11
Prol, proliferation; PBMC, peripheral blood mononuclear cells; Ag, antigen; IL-10, interleukin-10; TGF-, transforming growth
factor-; IFN-, interferon-; Tr, regulatory T cell.
1
Demonstration that Tr cells respond to the pathogen or pathogen antigens in vitro. 2Demonstration of CD4+ or CD8+ Tr cell clones
specific for pathogen antigens. 3Suppression of proliferation or cytokine production by indicate cells (in vitro unless otherwise stated).
Table 2. Role of CD4+ CD25+ Tr cells in infection
Pathogen
Species
Agspecific1
Cytokine
secreted
Tr cells suppress2
Innate responses in vivo
Manipulation of
CD25+ Tr cells
Transfer
In vitro depletion
Effect on immune response,
immunopathology and pathogen burden
prevents H. hepaticis induced intestinal
inflammation (reversed by anti-IL-10 or
anti-TGF-); no effect on bacterial
colonization.
reduces liver damage and increases survival
decreases IFN- secreting cells in vivo and
increases fungal burden
increases pathogen load
enhances non-healing skin lesions and
increases parasite burden
enhances Ag-specific lymph node IFN-
and IL-4 and severity of colon lesions and
increases parasite load
enhances Th1 response, CD4+ T cell
infiltration and stromal keratitis
enhances spleen cell prol and decreases
parasite burden
decreases parasite burden
enhances CD4+ T cell IFN- and gastritis
and decreases bacterial load
enhances Ag-specific T cell prol
In vitro depletion
enhances HIV-specific CD8 T cell IFN-
Helicobacter hepaticus
Mouse
Schistosoma mansoni
Candida albicans
Mouse
Mouse
Pneumocystis carnii
Leishmania major
Mouse
Mouse
Leishmania major
Mouse
Herpes simplex virus
Mouse
Plasmodium yoelii
Mouse
In vivo depletion
Plasmodium berghei
Helicobacter pylori
Mouse
Mouse
In vivo depletion
In vivo depletion
Helicobacter pylori
Human
HIV
Human
Yes
IL-10
IL-10, IL4, TGF-
Naïve T cell prol
IL-10
CD25- cells prol + IFN in vitro + in vivo
IL-10
Ag-specific CD4 IFN-
Ag-specific
CD25low
cell prol + IFN-
Ag-specific CD4 +
CD8 prol + cytokines
Transfer
Transfer
Transfer
Transfer to IL-10-/or wild-type
Depletion
from
spleen cells prior to
SCID transfer
In vivo depletion
Refs
37
77
70
69
29
78
62
91
92
68
30
81,82
Prol, proliferation; Ag, antigen; IL-10, interleukin-10; TGF-, transforming growth factor-; IFN-, interferon-; Tr, regulatory T cell.
1
Demonstration that Tr cells respond to the pathogen or pathogen antigens in vitro (none of these studies generated antigen-specific
CD4+ CD25+ Tr cell clones). 2Suppression of proliferation or cytokine production by indicate cells (in vitro unless otherwise stated).