title: CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses.
abstract: CD1d-restricted NKT cells are a novel T cell lineage with unusual features. They co-express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN-gamma and IL-4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d-restricted NKT cell activation in the induction of B cell-mediated immune responses to infection is still unclear. We show here that CD1-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite-specific antibody formation in response to Plasmodium berghei infection. The increased B cell-mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)-anchored protein merozoite surface protein 1 (MSP-1) were found to be significantly lower in CD1(-/-) mice compared to wild-type animals. P. berghei-infected MHC class II (MHCII)(-/-) mice also generated antibodies against MSP-1, suggesting that antibody production against GPI-anchored antigens in response to malaria infection can arise from both MHCII-dependent and independent pathways.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. hansen@wehi.edu.au
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Siomos
authors.forename: Tania
authors.initials: T
authors.lastname: De Koning-Ward
authors.forename: Lynn
authors.initials: L
authors.lastname: Buckingham
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008288:Malaria / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology / Q000378:metabolism; D013163:Splenomegaly / Q000276:immunology / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M