Inter-mouse strain differences in the in vivo anti-CD3 induced cytokine release.
Triggering of the CD3 molecule by in vivo injection of the hamster anti-murine CD3 monoclonal antibody 145-2C11 in adult BALB/c mice leads to massive although transient T cell activation. High levels of tumour necrosis factor (TNF), interferon-gamma (IFN-gamma), IL-2, IL-3 and IL-6 are released into the circulation 1 to 8 h after a single 10 micrograms 145-2C11 i.v. injection. This release induces an impressive self-limited physical reaction associating hypothermia, hypomotility (as assessed by actimetry), diarrhoea, piloerection and even death when high doses (a single dose of greater than 100 micrograms/mouse injection) are administered. In vivo injection of 145-2C11 to other selected mouse strains, namely NZW, CBA/J and C3H/HeJ, induced both different cytokine release patterns and sickness. 145-2C11 induced significant release of TNF and IL-2 in all four strains. At variance, IFN-gamma was only detected in BALB/c mice sera which, in terms of physical reaction (hypothermia and hypomotility) were the most affected. Higher and long-lasting circulating IL-3/GM-CSF levels were present in CBA/J sera, correlating with a later recovery. These results underline heterogeneity in the in vivo cell activation pattern among different mouse strains, when triggering T lymphocytes via the CD3/Ti molecule as compared to exclusive targeting of monocyte/macrophages by means of lipopolysaccharide.
Ferran
C
C
INSERM U 25, CNRS UA 122, Hôpital Necker, Paris, France.
Dy
M
M
Sheehan
K
K
Merite
S
S
Schreiber
R
R
Landais
P
P
Grau
G
G
Bluestone
J
J
Bach
J F
JF
Chatenoud
L
L
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D017252:CD3 Complex; D015704:CD4 Antigens / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006636:Histamine Release; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology*; D008808:Mice, Inbred CBA / Q000276:immunology*; D008811:Mice, Inbred DBA / Q000276:immunology*; D008819:Mice, Nude / Q000276:immunology*; D009043:Motor Activity / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor