Am. J. Respir. Crit. Care Med., Vol 153, No. 1, 01 1996, 102-109.
Pretreatment with allergen prevents immediate hypersensitivity and airway hyperresponsiveness
A Oshiba, E Hamelmann, KL Bradley, JE Loader, H Renz, GL Larsen and EW Gelfand
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
The ability of subcutaneous pretreatment with an immunogenic peptide
derived from Fel d I, the major cat protein, to suppress the development of
allergic responses was examined in a mouse model of antigen-induced
sensitization. BALB/c mice exposed to aerosolized Fel d I chain 1 peptide
developed antigen-specific IgE responses, immediate cutaneous reactivity to
the peptide, and increased airway responsiveness (AR). Both subcutaneous
and intraperitoneal administration of the peptide prior to sensitization
caused a 50% reduction in cutaneous reactivity which was associated with a
decrease in serum anti-Fel d I chain 1 IgE and IgG1 antibody responses and
an increase in specific IgG. Pretreatment with the peptide also suppressed
spleen and lymph node proliferative responses to the peptide. However, only
subcutaneous peptide injections could prevent the development of increased
AR. Transfer of spleen cells from subcutaneously peptide- treated mice to
sensitized recipients reduced serum antigen-specific IgE and IgG1 antibody
responses and skin test reactivity, and prevented alterations in AR. These
data suggest that IgE (and IgG1) responses and airway hyperresponsiveness
induced by allergen sensitization via the airways can be modulated by
subcutaneous administration of peptide. Further, the results define a model
for investigating the modulatory effects of subcutaneous administration of
immunogenic peptides or protein on an ongoing allergic response.