Nippostrongylus brasiliensis can induce B7-independent antigen-specific development of IL-4-producing T cells from naive CD4 T cells in vivo.
Th2 immune responses to a number of infectious pathogens are dependent on B7-1/B7-2 costimulatory molecule interactions. We have now examined the Th2 immune response to Nippostrongylus brasiliensis (Nb) in B7-1/B7-2(-/-) mice and show that Th2 effector cells develop that can mediate worm expulsion and produce substantial Th2 cytokines comparable with wild-type infected mice; however, in marked contrast, B cell Ag-specific Ab production is abrogated after B7 blockade. To examine the mechanism of T cell activation, OVA-specific DO11.10 T cells were transferred to recipient mice, which were then immunized with a combination of Nb plus OVA or either alone. Only the combination of Nb plus OVA triggered T cell differentiation to OVA-specific Th2 cells, suggesting that Nb acts as an adjuvant to stimulate Ag-specific naive T cells to differentiate to effector Th2 cells. Furthermore, using the DO11.10 TCR-transgenic T cell adoptive transfer model, we show that blocking B7-1/B7-2 interactions does not impair nonparasite Ag-specific DO11.10 Th2 cell differentiation; however, DO11.10 T cell cycle progression and migration to the B cell zone are inhibited.
Liu
Zhugong
Z
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Liu
Qian
Q
Pesce
John
J
Whitmire
Jeannette
J
Ekkens
Melinda J
MJ
Foster
Anthony
A
VanNoy
Jansie
J
Sharpe
Arlene H
AH
Urban
Joseph F
JF
Gause
William C
WC
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000097:blood; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D006131:Growth Inhibitors / Q000008:administration & dosage; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000096:biosynthesis*; D007399:Interphase / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009559:Nippostrongylus / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology
D000909:Antibodies, Helminth; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; C111390:OVA 323-339; D010446:Peptide Fragments; D015847:Interleukin-4; D000069594:Abatacept; D010047:Ovalbumin