H. polygyrus: B7-independence of the secondary type 2 response.
The gastrointestinal nematode parasite, Heligmosomoides polygyrus, has been used extensively in experimental studies of host immunity. The pronounced type 2 primary immune response to H. polygyrus is associated with elevated CD4+, TCR-alpha/beta + T cell IL-4 production and elevated serum IgE levels that are blocked by inhibiting CD28/ CTLA4-B7 interactions following in vivo administration of the chimeric fusion protein, CTLA4Ig. In the present study, we have examined the in vivo effects of blocking CTLA4Ig ligands on the secondary type 2 mucosal host protective immune response to this parasite. Our results show that although CD4+, TCR-alpha/beta + cells remain the primary source of elevated IL-4 during the secondary response, the protective immune response and the effector cell activity associated with it is B7-independent as CTLA4Ig administration at the time of challenge does not block (1) elevations in T cell IL-4 gene expression or protein secretion; (2) elevations in serum IgE levels, mucosal mastocytosis, or eosinophilia; or (3) host protection, as measured by adult worm burden and fecundity. These findings suggest that memory T helper cells do not require CD28-B7 interactions for their activation to effector cells that can mediate a host protective type 2 immune response.
Gause
W C
WC
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Lu
P
P
Zhou
X D
XD
Chen
S J
SJ
Madden
K B
KB
Morris
S C
SC
Linsley
P S
PS
Finkelman
F D
FD
Urban
J F
JF
D000069594:Abatacept; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004802:Eosinophilia; D005260:Female; D018928:Immunity, Mucosal; D018796:Immunoconjugates; D007073:Immunoglobulin E / Q000097:blood; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017206:Strongylida Infections / Q000276:immunology*
D000909:Antibodies, Helminth; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D015848:Interleukin-5; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007073:Immunoglobulin E; D000069594:Abatacept