Allergen recognition in the origin of asthma

Allergic respiratory diseases such as bronchial asthma are believed to result directly from the repeated local expression in airway tissues of T helper (Th) 2-polarized T cell immunity to inhaled allergens. Recent evidence suggests that these T cell responses are typically primed in utero and subsequently reshaped during postnatal allergen exposure via immune deviation, leading to the eventual emergence of stable allergen-specific T cell memory which is polarized towards the Th1 (normal) or Th2 (atopic) phenotype. The underlying Th1/Th2 switching process is influenced by a number of host and environmental factors that are poorly understood. Prominent amongst these are factors that affect the kinetics of maturation of immune competence during the early postnatal period. In particular, there is mounting evidence that the immunological milieu at the materno-fetal interface is naturally skewed towards the Th2 phenotype (possibly an evolutionary adaptation to protect the placenta against the toxic effects of Th1 cytokines). Furthermore, this bias appears to be preserved for varying periods into infancy, which may account for the presence of a high risk 'window' for allergic sensitization in early postnatal life. It is hypothesized that the principal impetus for postnatal development of a normal Th1/Th2 balance (and hence closure of the high risk sensitization window) is provided via contact with Th1-stimulatory commensal and pathogenic micro-organisms at the body's major mucosal surfaces

Regulation of T-helper cell responses to inhalant allergen during early childhood

Background Recent evidence suggests that preschool children manifest patterns of allergen-specific skin prick test (SPT) reactivity and in vitro T-cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli

Inhalant allergen-specific T-cell reactivity is detectable in close to 100% of atopic and normal individuals: covert responses are unmasked by serum-free medium

It is widely held that in vitro T cell responses to allergens are more prominent in atopic than in normal individuals, though this conclusion is based upon culture techniques which fail to detect proliferative responses in a significant minority of atopics and many normals.Study allergen-specific proliferative responses of T cells cultured in serum-free medium (SFM). Examine associations between atopic status, age and T cell reactivity.Initially, peripheral blood mononuclear cells were stimulated with allergens or antigens in SFM, and compared with cells cultured in RPMI + 10% fetal calf serum or human AB serum. Subsequently, T cell reactivity was studied in 34 adults (20-49 years), 27 children (2-13 years), and 19 infants (< or = 10 weeks) using SFM alone.Compared with serum-supplemented medium, SFM enhanced net T cell proliferation, both in bulk culture and when cloning at limiting dilution. In many subjects, SFM unmasked T cell reactivity to allergens which was not otherwise evident, and lowered the threshold allergen levels required for in vitro T cell triggering. For most allergens, T cell proliferative responses did not differ between adults who had specific IgE, and those who did not. The most vigorous responses observed were to ubiquitous inhalant allergens, which stimulated T cells from close to 100% of adults and children, and over 60% of infants. In contrast, responses to the 'vaccine' antigen tetanus toxoid were completely absent in the latter age group, but present in the majority of adults and children.These findings suggest that the extent of active T cell recognition of environmental allergens has been hitherto underestimated, and further that these responses may frequently be initiated in very early life. Additionally, these findings reinforce the notion that qualitative (as opposed to quantitative) variations in specific T cell reactivity ultimately determine allergen responder phenotype

Atopic versus infectious diseases in childhood: a question of balance?

There is an increasing interest in the concept that respiratory tract infections during early childhood may in some circumstances confer protection against sensitisation to aeroallergens, via 'bystander' stimulation of Th-1 associated immune functions in the regional lymph nodes draining the air way mucosa. We hypothesise below that this phenomenon may be but one component of a broader process operative during early postnatal life, in which generalised contact with the microbial environment plays an obligatory role in stimulating the functional maturation of the Th-1 arm of the immune response. We argue further that one of the most potent sources of such stimulation is provided by the normal commensal flora of the gastrointestinal tract, which is establish during early infancy