Enterotoxin adjuvants have direct effects on T cells and antigen-presenting cells that result in either interleukin-4-dependent or -independent immune responses.
In an in vitro study, Escherichia coli heat-labile toxin (LT) was shown to directly affect activated CD4(+) T cells and support interleukin (IL)-5 production in IL-4-deficient (IL-4(-/-)) mice, whereas cholera toxin (CT) did not. Both LT and CT enhanced B7-2 expression on B cells and macrophages. These effects were not influenced by CD40-CD40 ligand cosignaling. Addition of LT- or CT-treated antigen-presenting cells to anti-CD3-triggered CD4(+) T cells resulted in the induction of T cell proliferative responses. Further, these responses were inhibited by anti-B7-2 monoclonal antibody. Cocultivation of CD4(+) T cells with LT- or CT-treated antigen-presenting cells and anti-CD3 enhanced Th1- and IL-4-mediated Th2-type cytokine production. The results from in vitro studies were supported by in vivo studies in IL-4(-/-) mice, in which LT induced mucosal IgA responses but CT did not. Thus, although both LT and CT induce mucosal adjuvant responses via IL-4-dependent Th2-type responses, LT also elicits Th1- and IL-4-independent Th2-type responses.
Yamamoto
M
M
Department of Clinical Pathology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Kiyono
H
H
Kweon
M N
MN
Yamamoto
S
S
Fujihashi
K
K
Kurazono
H
H
Imaoka
K
K
Bluethmann
H
H
Takahashi
I
I
Takeda
Y
Y
Azuma
M
M
McGhee
J R
JR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D001427:Bacterial Toxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; D001427:Bacterial Toxins; C497965:Cd86 protein, mouse; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C037420:stN protein, Vibrio cholerae; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C027538:heat-labile enterotoxin, E coli