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The role of CTLA-4 and a mucosal adjuvant cholera toxin in oral sensitization to peanut
S234 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
MONDAY 835
The Role of CTLA-4 and a Mucosal Adjuvant Cholera Toxin in Oral Sensitization to Peanut
F. van Wijk1, S. Hoeks1, L. Knippels2, L. Boon3, S. Koppelman4, R. Pieters1; 1Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht, NETHERLANDS, 2Experimental Immunology, TNO Nutrition
J ALLERGY CLIN IMMUNOL VOLUME 113, NUMBER 2
Abstracts S235
MONDAY
and Food Research, Zeist, NETHERLANDS, 3Bioceros B.V., Amsterdam, NETHERLANDS, 4Protein Technology, TNO Nutrition and Food Research, Zeist, NETHERLANDS. RATIONALE: Animal models can be useful to determine the early inducing factors in sensitization to food proteins. We investigated the role of the co-stimulatory molecule CTLA-4 in sensitization to peanut. METHODS: An established oral peanut allergy model (C3H/HeOuJ mice) was used to measure antibody and cytokine responses against peanut (PE) and the purified peanut allergens Ara h1, Ara h2 and Ara h3. During the sensitization protocol, with or without cholera toxin (CT) as adjuvant, the inhibitory co-stimulatory molecule CTLA-4 (clone 4F-10) was blocked. RESULTS: After 1 week of exposure to PE plus CT, a diverse pattern of antigen induced cytokine production (IL-4, IL-5, IL-10 and IFN-gamma) was found in the spleen, leading to sensitization (antigen-specific IgE) from week 3. However, without CT, specific early cytokine production was completely absent and only low levels of IgG1 and no IgE antibody production were observed. Blocking CTLA-4 during PE plus CT exposure induced a dramatic upregulation of TH2 cytokine production in the spleen and an elevation of total and PE/Ara h-specific IgE compared to the PE plus CT treated group. When CTLA-4 was blocked during PE exposure without CT, a similar increase in Th2 cytokine and total IgE production compared to the PE dosed animals was found but no PE/Ara h-specific IgE could be detected in these mice. CONCLUSIONS: These results suggest a role for CTLA-4 in suppressing TH2 responses to food proteins and furthermore implicate that cytokine production is required to induce sensitization but is only effective in combination with an adjuvant. Funding: Institute for Risk Assessment Sciences, Utrecht University
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
MONDAY 835
The Role of CTLA-4 and a Mucosal Adjuvant Cholera Toxin in Oral Sensitization to Peanut
F. van Wijk1, S. Hoeks1, L. Knippels2, L. Boon3, S. Koppelman4, R. Pieters1; 1Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht, NETHERLANDS, 2Experimental Immunology, TNO Nutrition
J ALLERGY CLIN IMMUNOL VOLUME 113, NUMBER 2
Abstracts S235
MONDAY
and Food Research, Zeist, NETHERLANDS, 3Bioceros B.V., Amsterdam, NETHERLANDS, 4Protein Technology, TNO Nutrition and Food Research, Zeist, NETHERLANDS. RATIONALE: Animal models can be useful to determine the early inducing factors in sensitization to food proteins. We investigated the role of the co-stimulatory molecule CTLA-4 in sensitization to peanut. METHODS: An established oral peanut allergy model (C3H/HeOuJ mice) was used to measure antibody and cytokine responses against peanut (PE) and the purified peanut allergens Ara h1, Ara h2 and Ara h3. During the sensitization protocol, with or without cholera toxin (CT) as adjuvant, the inhibitory co-stimulatory molecule CTLA-4 (clone 4F-10) was blocked. RESULTS: After 1 week of exposure to PE plus CT, a diverse pattern of antigen induced cytokine production (IL-4, IL-5, IL-10 and IFN-gamma) was found in the spleen, leading to sensitization (antigen-specific IgE) from week 3. However, without CT, specific early cytokine production was completely absent and only low levels of IgG1 and no IgE antibody production were observed. Blocking CTLA-4 during PE plus CT exposure induced a dramatic upregulation of TH2 cytokine production in the spleen and an elevation of total and PE/Ara h-specific IgE compared to the PE plus CT treated group. When CTLA-4 was blocked during PE exposure without CT, a similar increase in Th2 cytokine and total IgE production compared to the PE dosed animals was found but no PE/Ara h-specific IgE could be detected in these mice. CONCLUSIONS: These results suggest a role for CTLA-4 in suppressing TH2 responses to food proteins and furthermore implicate that cytokine production is required to induce sensitization but is only effective in combination with an adjuvant. Funding: Institute for Risk Assessment Sciences, Utrecht University