Contribution of mast cells to the T helper 2 response induced by simultaneous subcutaneous and oral immunization

Abstract

This work examines the contribution of mast cells to the synergistic enhancement of the T helper 2 (Th2) immune response elicited following simultaneous oral and subcutaneous (s.c.) immunization. The s.c. route induced a Th1-biased immune response, characterized by increased interferon-gamma (IFN-gamma) and immunoglobulin G2a (IgG2a) antibody production. In contrast, oral immunization stimulated a primarily Th2-type response in which interleukin-4 (IL-4) and IgG1 antibody production were dominant. Simultaneous immunization also triggered a Th2-biased response, the magnitude of which exceeded the additive effects of s.c. and oral immunization alone by greater than threefold. To analyse whether mast cells in gut-associated lymphoid tissue contributed to this synergistic response, mast cell-deficient mice WBB6F1-w/wv were studied. Whereas the primary response following simultaneously antigen administration was reduced only twofold in these animals compared with wild type controls WBB6F1-+/+ (suggesting that mast cells were not needed to initiate Th2 immunity), reconstitution with bone-marrow-derived mast cells from WBB6F1-+/+ mice resulted in a superoptimal response (suggesting that mast cells contribute to the magnitude and perpetuation of these Th2-biased responses).

Figure 1

Co‐operative and synergistic effct of simultaneous s.c. and oral immunization. BALB/c mice were immunized with 100 µg OVA s.c. (day 0). Certain mice received with 10 mg OVA for four consecutive days (Day 0 to Day 3). Seven days after immunization (Day 6) the mice were killed and the spleen cells were analysed for anti‐OVA antibody‐producing cells employing ELIspot assay. The data are expressed as antibody producing spots number per 10⁶ spleen cells ± standard error (SE). *P < 0·05 compared with either s.c. alone group or oral alone group.

Figure 2

IL‐4 and IFN‐γ producing cells in s.c. and oral immunization. IL‐4 and IFN‐γ producing cells are enumerated by ELTspot assay. The data are expressed as antibody‐producing spots number per 10⁶ spleen cells ± standard error (SE). In IL‐4 production *P < 0·05 compared with the responses of both s.c. alone group and oral alone group. In IFN‐γ production *P < 0·05 compared with either oral alone group or s.c. plus oral group.

Figure 3

Proposed model of Th2 cell differentiation.