Depletion of CD4+CD25+ T cells switches the whey-allergic response from immunoglobulin E- to immunoglobulin free light chain-dependent.
BACKGROUND
Symptoms of allergy are largely attributed to an IgE-mediated hypersensitivity response. However, a considerable number of patients also exhibit clinical features of allergy without detectable systemic IgE. Previous work showed that Ig-free light chains (IgLC) may act as an alternate mechanism to induce allergic responses. CD4+CD25+ T cells are crucial in the initiation and regulation of allergic responses and compromised function might affect the response to allergens.


OBJECTIVE
To examine the contribution of CD4+CD25+ T cells and IgLC towards the whey-allergic response.


METHODS
Mice were sensitized orally with whey using cholera toxin as an adjuvant. CD25+ T cells were depleted in vivo using a CD25 mAb. The acute allergic skin response to whey and ex vivo colon reactivity was measured in the presence or absence of F991, a specific inhibitor of IgLC. Serum whey-specific antibodies and IgLC in serum and mesenteric lymph node (MLN) supernatants were measured. Depletion of CD4+CD25+ T cells was confirmed in the spleen.


RESULTS
Anti-CD25 treatment strongly reduced whey-specific antibody levels and resulted in a partial depletion of effector T cells and a major depletion of Foxp3(+) regulatory T cells. Surprisingly, despite the abolished specific IgE response, the acute allergic skin response to whey was not affected. IgLC levels were enhanced in the serum and MLN supernatants of CD25-depleted sensitized mice. F991 inhibited the acute skin response and colon hyperreactivity in anti-CD25-treated mice, indicating that these responses were mainly IgLC dependent.


CONCLUSIONS
Depletion of CD4+CD25+ T cells resulted in a switch from an IgE- to an IgLC-dependent acute skin response and functional hyperresponsiveness of the colon. Our data suggest that CD25+ T cells play a crucial role in balancing cow's milk allergy between IgE and IgE-independent responses and both mechanisms might play a role in allergic responses to the same allergen.
van Esch
B C A M
BC
Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Sorbonnelaan 16, Utrecht, The Netherlands.
Schouten
B
B
Blokhuis
B R J
BR
Hofman
G A
GA
Boon
L
L
Garssen
J
J
Knippels
L M J
LM
Willemsen
L E M
LE
Redegeld
F A
FA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D007073:Immunoglobulin E / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016269:Milk Hypersensitivity / Q000276:immunology*; D008894:Milk Proteins / Q000009:adverse effects / Q000276:immunology; D000067816:Whey Proteins
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D053645:Interleukin-2 Receptor alpha Subunit; D008894:Milk Proteins; D000067816:Whey Proteins; D007073:Immunoglobulin E