| Abstract
| - Difficulties in detecting human IL-4 synthesis in antigen-driven primary culture have led to widespread reliance on less physlologic appraoches to T cell activation. Although there is general agreement of a T 2-like blas,l the precise defects in ctokine responsiveness remain controverslal. Analysis of cytokine protein production by fresh, unselected cell populations in response to gognate, antigen-driven stimulation remains an important goal. Here, limitting dilution analysis (LDA) was sued to evaluate antigen-stimulated cytokine gene expression by fresh peripheral blood mononuclear cells(PBMC)(.PBMC from 19 grass pollen sensitive, allergic rhinitis subjects and normal, non-atopic contrls were evaluated 1 mont after natural relmmunization (the peak of te local grass pollen season). Surprisingly, highly atopic subjects and cllnically non-allergic individuals exhiboited virtually equlvalent antigen-specific, CD4-dependent cytokine production in response to short-term culture with these common environmental antigens. As anticipated, pronounced increases in Th2-like activity were evidnet in te circulating immune repertolre of grass of 117:1 among normal subjects versus 4:1 among those with allergic rhinitis (Mann-Whitney U-test, P=0.0067). This Th2-like blas reflected both a lower frequencey of IFN-γprducing cells and a markedly increased frequency of IL-4-producing cells in the circulatin grass-pollen specific repertoire of atopic donors. The observation that every atopic and normal subject produced IFN-γ (±IL-4) following antigen re-stimulation arguses that the decision as to whether allergy or (clinical) tolerance results, hinges not on a genetically determined capacity of whether allergen-reactive T cells can be stimulated in any given individual by cronic exposure to ubiqultous enveronmental antigens, but on the nature of the cokine response that comes to dominate that individual's response
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