CTLA-4 ligands are required to induce an in vivo interleukin 4 response to a gastrointestinal nematode parasite.
The costimulatory signal provided to T cells through CTLA-4-ligand interactions is required for T cell activation resulting in increased interleukin 2 (IL-2) production in vitro, but its role in the production of IL-4 and other cytokines is unclear and few in vivo studies have been performed to confirm results of in vitro experiments. We have examined the in vivo effects of blocking CTLA-4 ligands on the T helper cell 2 (Th2)-associated mucosal immune response that follows oral infection of mice with the nematode parasite, Heligmosomoides polygyrus. CTLA-4Ig administration inhibited H. polygyrus-induced increases in mesenteric lymph node (MLN) B cell major histocompatibility complex class II expression and size and T cell-derived IL-4 gene expression. In addition, CTLA-4 immunoglobulin (Ig) partially blocked increased IL-3, IL-5, and IL-9 cytokine gene expression in Peyer's patch (PP) and MLN 8 d after primary inoculation of mice with the parasite. Increases in the number of IL-4- but not IL-5-secreting cells were also inhibited by CTLA-4Ig. H. polygyrus-induced elevations in serum IgE levels but not blood eosinophils, were markedly inhibited by CTLA-4Ig. These results suggest that stimulation of CD28 and/or CTLA-4 is required for T cell priming leading to IL-4 cytokine production, B cell activation, and IgE secretion during a Th2-like, mucosal immune response to a nematode parasite.
Lu
P
P
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Zhou
X
X
Chen
S J
SJ
Moorman
M
M
Morris
S C
SC
Finkelman
F D
FD
Linsley
P
P
Urban
J F
JF
Gause
W C
WC
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D006369:Heligmosomatoidea / Q000276:immunology*; D018796:Immunoconjugates; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D000069594:Abatacept