Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity

TY - JOUR

T1 - Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity

AU - Nouri-Aria, Kayhan T

AU - Wachholz, Petra A

AU - Francis, James N

AU - Jacobson, Mikila R

AU - Walker, Samantha M

AU - Wilcock, Louisa K

AU - Staple, Steven Q

AU - Aalberse, Robert C

AU - Till, Stephen J

AU - Durham, Stephen R

PY - 2004/3/1

Y1 - 2004/3/1

N2 - T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA(+) cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively, whereas only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10. Following immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG "blocking" activity correlated with the patients' overall assessment of improvement. Thus, grass pollen immunotherapy may induce allergen-specific, IL-10-dependent "protective" IgG4 responses.

AB - T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA(+) cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively, whereas only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10. Following immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG "blocking" activity correlated with the patients' overall assessment of improvement. Thus, grass pollen immunotherapy may induce allergen-specific, IL-10-dependent "protective" IgG4 responses.

KW - Interleukin-10

KW - Double-Blind Method

KW - Humans

KW - Desensitization, Immunologic

KW - Plant Proteins

KW - B-Lymphocytes

KW - Pollen

KW - Phleum

KW - Immune Sera

KW - RNA, Messenger

KW - Antibodies, Blocking

KW - Cells, Cultured

KW - Rhinitis, Allergic, Seasonal

KW - Allergens

KW - Adult

KW - Binding, Competitive

KW - Immunoglobulin G

KW - Nasal Mucosa

KW - Up-Regulation

KW - Male

KW - Female

U2 - 10.4049/​jimmunol.172.5.3252

DO - 10.4049/​jimmunol.172.5.3252

M3 - Article

C2 - 14978133

SN - 0022-1767

VL - 172

SP - 3252

EP - 3259

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -