Elicitation of nickel sulfate (NiSO4)-specific delayed-type hypersensitivity requires early-occurring and early-acting, NiSO4-specific DTH-initiating cells with an unusual mixed phenotype for an antigen-specific cell.

The elicitation in immunized mice of delayed-type hypersensitivity (DTH) responses to nickel sulfate (NiSO4) was found to be mediated by the sequential activities of two different antigen-specific Thy-1+ cells. Early-acting (2-hr) NiSO4-specific, DTH-initiating cells were required for elicitation of subsequent 24-hr NiSO4-specific DTH and had an unusual phenotype for an antigen-specific cell (Thy-1+, CD5+, CD3-, CD4-, CD8- CD23+, CD45RA+ (B220+), IL-2R-, IL-3R+, sIg-, MHC Class II-, Mel-14-, CD44+ (Pgp-1+), J11d+ (HSA+), MAC-1+, LFA-1, and Fc gamma II-R+). In contrast, the late-acting, NiSO4-specific DTH-effector T cells were: Thy-1+, CD5+, CD3+, CD4+, CD8-, CD23-, B220-, IL-2R+, IL-3R-, sIg-, MHC Class II-, Mel-14+, CD44- (Pgp-1-), J11d- (HSA-), MAC-1-, LFA-1+, and Fc gamma II-R-. Our results led us to surmise that the early-acting DTH-initiating cells were necessary to locally recruit the late-acting effector T cells. Relatively high doses of anti-B220 (CD45RA) and anti-CD23 (IgE Fc epsilon RII receptor) monoclonal antibodies were necessary to completely eliminate all DTH-initiating cells, and therefore completely block subsequent expression of some late NiSO4-specific DTH activity that was due to the late-acting DTH effector T cells. In addition, we found that mast cells were important for expression of early-acting, DTH-initiating cell activity in this NiSO4-specific, DTH system. This was probably due to the absence of mast cells in mast cell-deficient WBB6F1-W/Wv mice. Our results indicated that two different antigen-specific Thy-1+ cells are necessary to elicit NiSO4-specific DTH in mice and that mast cells are necessary for expression of the early component that is due to early-acting, DTH-initiating cells.