CONTRIBUTION OF CD4(-LYMPHOCYTE SUBSETS TO THE CYTOKINE SECRETION PATTERNS INDUCED IN MICE DURING SENSITIZATION TO CONTACT AND RESPIRATORY CHEMICAL ALLERGENS() AND CD8(+) T)

Chemical allergens of different types, those that cause in humans alle rgic contact dermatitis or occupational asthma, induce in mice diverge nt immune responses characteristic, respectively, of T-helper 1 (Th1)- and Th2-type cell activation. Such responses are associated with the development of different cytokine secretion patterns by draining lymph node cells (LNC), such that contact allergens stimulate vigorous inte rferon-gamma (IFN-gamma) production, but little secretion of the Th2 c ytokines interleukin-4 and interleukin-10 (IL-4 and IL-10), whereas th e converse pattern is provoked by respiratory allergens. Using selecti ve depletion with antibody and complement we have here examined the re lative contribution of CD4(+) and CD8(+) T lymphocytes to the cytokine secretion patterns of draining LNC isolated from mice sensitized to c hemical allergens. Mice received repeated topical applications of resp iratory allergens, trimellitic anhydride (TMA) or diphenylmethane diis ocyanate (MDI), or of contact allergens 2,4-dinitrochlorobenzene (DNCB ) or formaldehyde. Thirteen days following the initiation of exposure the production by draining LNC of IL-10, IFN-gamma and mitogen (concan avalin A)-inducible IL-4 was measured by enzyme-linked immunosorbent a ssay (ELISA) after various periods of culture. It was found that the h igh levels of IL-4 and IL-10 secretion stimulated by TMA or MDI, and t he lower levels of these cytokines induced by DNCB or formaldehyde, we re in all cases dependent upon the presence of CD4(+) cells. In contra st, the comparatively high concentrations of IFN-gamma observed follow ing exposure to contact allergens were found to be derived from CD4(+) cells, and in the case of DNCB from CD8(+) cells also. The low levels of IFN-gamma induced by treatment with TMA or MDI were associated lar gely or wholly with CD8(+) cells. These data indicate that the type 2 cytokine responses induced to different extents by both contact and re spiratory chemical allergens are almost exclusively a function of CD4( +) cells, but that IFN-gamma is produced by either CD4(+) and CD8(+) c ells in the case of contact allergens or largely by CD8(+) cells in th e case of chemical respiratory allergens.