January 31, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Prof. Jacques Louis
Immunity against intracellular pathogens
Lecture :
January 24 – February 5, 2005 at the Institut Pasteur in Ho Chi Minh City, Vietnam
with kind support from ANRS & Université Pierre et Marie Curie
Jointly organized by Institut Pasteur in Ho Chi Minh City and Institut Pasteur
Basis of Immunology and Immunophysiopathology of Infectious Diseases
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
1
10
100
1
10
100
0
0
50
50
50
100
C57BL/6
150 0
50
50
100
150 0
50
Hours after injection with LACK
150 0
IL-2 IL-4
100
100
150
150
C57BL/6 anti-IFN-γ
Hours after infection with L. major
150 0
IL-2 IL-4
100
100
BALB/c
Kinetics of IL-2 and IL-4 mRNA expression following infection with L. major or injection of LACK
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Fold increase in mRNA
1
10
100
1
10
100
Control Anti-IL-2
Control Anti-IL-2
BALB/c
Control Anti-IL-2
Control Anti-IL-2
C57BL/6
Control Anti-IL-2
Control Anti-IL-2
C57BL/6 anti-IFN-γ
LACK
L. major
Importance of the early IL-2 response on the rapid IL-4 mRNA expression in susceptible mice
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Fold increase in mRNA
0
2
4
6
0
20
30
40
days of infection
10
BALB/c BALB/c anti-IL-2 BALB/c anti-IL-2 + rIL-4
50
0
10
BALB/c anti-IL-2 + rIL-4
BALB/c anti-IL-2
BALB/c
4
10
6
10
8
10
L. major per footpad
2
10
Treatment with anti-IL-2 Ab renders otherwise susceptible BALB/c mice resistant to L. major
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Lesion size (mm)
1
1
10
10
1
10
100
1
10
10
100 1
10
Fold increase in IL-4 mRNA expression
100 1
LACK
L. major
100
100
C57BL/6 anti-IFN-γ
Fold increase in IL-2 mRNA expression
100
LACK
L. major
C57BL/6
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
CD3- CD19-
CD3- CD19+
CD3+ CD4-
CD3+ CD4+ Vβ4-
CD3+ CD4+ Vβ4+
CD3- CD19-
CD3- CD19+
CD3+ CD4-
CD3+ CD4+ Vβ4-
CD3+ CD4+ Vβ4+
BALB/c
Cellular source of the rapid IL-2 mRNA expression
0
2
4
0
2
4
0
25
50
n.r.
75
10 8 non-depleted
0
25
50
75
100
Days of infection with L. major
100
BALB/c
10 8 V β 4-depleted
0
25
50
C57BL/6
75
10 8 V β 6-depleted
SCID mice reconstituted with normal syngeneic spleen cells depleted of Vβ4+ CD4+ cells are resistant to L. major
100
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Lesion size (mm)
1
1
1
1
10
10 IL-4 mRNA
n.d.
IL-4 mRNA
Fold increase in
100
100
IL-2 mRNA
10
10 IFN-γ mRNA
n.d.
n.d.
100
100
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
10 8 non-depleted 10 8 Vβ4-depleted 10 8 Vβ6-depleted n.r. BALB/c C57BL/6
BALB/c
10 8 Vβ6-depleted n.r.
10 8 non-depleted 10 8 Vβ4-depleted
SCID mice reconstituted with normal spleen cells depleted in Vβ4+ cells do not mount early IL-4 responses and develop a TH1 response
1
10 IL-2 mRNA
n.d.
1
10 IL-4 mRNA
Fold increase in
100
n.d.
100
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
BALB/c
n.r.
10 8 Vβ4-depleted + 3x10 4 IL-2-/- Vβ4-Vα8 CD4 + 10 8 Vβ6-depleted
8 10 non-depleted 8 10 Vβ4-depleted 108 Vβ4-depleted + 3x10 4 IL-2 +/- Vβ4-Vα8 CD4 +
SCID mice reconstituted with Vβ4+-depleted normal spleen cells and IL-2-/- Vβ4-Vα8 CD4+ T cells do not mount an early IL-4 response. The presence of IL-2+/+ Vβ4-Vα8 CD4+ T cells allows the expression of this response
0
25
50
75
25
50
75
8 10 Vβ6-depleted
25
50
n.r.
75
100
108 V β 4-depleted + 3x104 IL-2+/-Vβ4-Vα 8 CD4+
100 0
8 10 Vβ4-depleted
Days after infection with L. major
100 0
108 Vβ 4-depleted + 3x104 IL-2 -/-Vβ4-Vα 8 CD4+
8 10 non-depleted
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
0
2
4
0 6
2
4
6
SCID mice reconstituted with Vβ4+-depleted normal spleen cells and IL-2-/- Vβ4-Vα8 CD4+ T cells are resistant to L. major. The presence of IL-2+/+ Vβ4-Vα8 CD4+ T cells allows the expression of a susceptible phenotype
Lesion size (mm)
1
n.d.
IL-2 mRNA
10
1
Fold increase in
100
n.d.
100 IL-4 mRNA
10
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
BALB/c
108 non-depleted 108 Vβ4-depleted 108 IL-2 +/- Vβ4-depleted + 3x104 IL-2 +/- Vβ4-Vα8 CD4+ 108 IL-2 -/- Vβ4-depleted + 3x104 IL-2 +/- Vβ4-Vα8 CD4+ 108 Vβ6-depleted n.r.
The expression of the early IL-4 response to L. major by Vβ4-Vα8 CD4+ requires that only these cells be also capable to produce IL-2
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Jacques Louis
UCSF • Richard Locksley
• Hayo Himmelrich • Alain Gumy • Pascal Launois
NOW at
University of Munich • Martin Röcken’s group
WHO Immunology Research and Training Center, Lausanne
Acknowledgements
