Scavenger receptor-specific allergen delivery elicits IFN-gamma-dominated immunity and directs established TH2-dominated responses to a nonallergic phenotype.
BACKGROUND
Immunotherapeutic approaches to allergy consist of reliably changing allergen-specific T(H)2 immunity associated with secretion of IL-4, IL-5, and IL-13, along with IgE antibodies in atopic individuals to T(H)1 immunity. Our earlier data show that targeting of protein antigens to antigen-presenting cells (APCs), such as macrophages, by means of scavenger receptors (SRs) results in a pronounced T(H)1 immunity. Here we demonstrate a novel experimental approach for the conversion of T(H)2 immunity to T(H)1 immunity by using SR delivery of allergens.


OBJECTIVE
We sought to show that targeting of allergens by means of SRs to APCs triggers T(H)1 immunity and that an established T(H)2 immunity to the Der p 1-immunodominant peptide 111-139 (p1, 111-139) can be modulated to a nonallergic T(H)1 phenotype.


METHODS
Analysis of the T cell-derived cytokines IL-4, IL-5, IL-13, and IFN-gamma in response to p1, 111-139 in C57BL/6 mice 7 to 42 days after immunization, measurement of specific antibody responses, eosinophilic infiltrate, and skin hypersensitivity in response to allergen challenge constitute the parameters of in vivo immunity.


RESULTS
We show that p1, 111-139, when delivered to APCs by means of SR, elicits a T(H)1-dominant immunity. If it is delivered to APCs either after chemical coupling to SR ligands or by means of mere coadsorption on alum in the presence of an SR ligand, the established T(H)2 immunity can be modified to T(H)1 immunity.


CONCLUSIONS
SR-mediated delivery of allergens has immunotherapeutic potential that may be usable in atopic individuals.
Bhatia
Sumeena
S
National Institute of Immunology, New Delhi, India.
Mukhopadhyay
Sangita
S
Jarman
Elizabeth
E
Hall
Gillian
G
George
Anna
A
Basu
Sandip K
SK
Rath
Satyajit
S
Lamb
Jonathan R
JR
Bal
Vineeta
V
D000818:Animals; D039741:Antigens, Dermatophagoides; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D016503:Drug Delivery Systems; D004804:Eosinophils; D006023:Glycoproteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000628:therapy*; D016056:Immunodominant Epitopes / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000276:immunology / Q000628:therapy; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012867:Skin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D039741:Antigens, Dermatophagoides; D016207:Cytokines; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D010455:Peptides; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D007371:Interferon-gamma