Adjuvant-Guided Type-1 and Type-2 Immunity: Infectious/Noninfectious Dichotomy Defines the Class of Response

TLDR

Traditionally, protein antigens are injected with CFA to elicit immunity and with IFA to induce tolerance. The study demonstrates that the adjuvant choice (CFA versus IFA) directs memory T‑cell differentiation into type‑1 or type‑2 cytokine profiles across seven antigens and six mouse strains, indicating that polarized immunity can be reliably achieved independent of host genetics and has broad implications for vaccine development.

Abstract

Traditionally, protein Ags have been injected in CFA (oil with inactivated mycobacteria) to induce immunity and with IFA (oil alone) to induce tolerance. We report here that injection of hen eggwhite lysozyme, a prototypic Ag, in CFA-induced and IFA-induced pools of hen eggwhite lysozyme-specific memory T cells of comparable fine specificity, clonal size, and avidity spectrum, but with type-1 and type-2 cytokine signatures, respectively. This adjuvant-guided induction of virtually unipolar type-1 and type-2 immunity was observed with seven protein Ags and in a total of six mouse strains. Highly polarized type-1 and type-2 immunity are thus readily achievable through the choice of adjuvant, irrespective of the genetic bias of the host and of the nature of the protein Ag. This finding should have far-reaching implications for the development of vaccines against infectious and autoimmune diseases. Furthermore, our demonstration that Ag injected with IFA is as strongly immunogenic for T cells as it is with CFA shows that the presence of the mycobacteria determines not the priming of naive T cells through the second-signal link but the path of downstream differentiation toward CD4 memory cells that express either type-1 or type-2 cytokines.