TH1 TH2 CELL DICHOTOMY IN ACQUIRED-IMMUNITY TO BORDETELLA-PERTUSSIS -VARIABLES IN THE IN-VIVO PRIMING AND IN-VITRO CYTOKINE DETECTION TECHNIQUES AFFECT THE CLASSIFICATION OF T-CELL SUBSETS AS TH1, TH2 OR TH0/

In studies of the mechanism of immunity to Bordetella per tussis in a murine respiratory infection model, we have previously demonstrated th at natural infection of immunization with a whole cell vaccine induces a potent protective immune response, which is mediated by T-helper ty pe-1 (Th1) cells. In contrast an acellular vaccine generates Th2 cells and is associated with delayed bacterial clearance following respirat ory challenge. In the present study we have investigated the apparent Th1/Th2 cell dichotomy in acquired immunity and have examined the fact ors that affect their induction or detection. The cytokine profiles of B. pertussis-specific T cells in immune animals were determined using antigen-stimulated ex vivo spleen cells or CD4(+) T-cell lines and cl ones established in the presence of interleukin-2 (IL-2) or IL-4. Anti gen-specific T cells derived from mice immunized with the acellular va ccine were almost exclusively of the Th2 cell type. In contrast, T-cel l lines and clones established following respiratory infection or immu nization with the whole cell vaccine were predominantly of the Th1 typ e. However, a proportion of T cells from convalescent mice, especially when cultured in the presence of IL-4, secreted IL-4 and IL-5 with or without detectable IL-2 and interferon-gamma (IFN-gamma), suggesting that Th0 or Th2 cells were also primed during natural infection in viv o. Furthermore, when mice were assessed 6 months after infection, sple en cells produced significant levels of IL-4 and IL-5, which were not evident at 6 weeks. The route of immunization and the genetic backgrou nd of the mice were also found to influence the preferential priming o f Th1 cells, and this was directly related to the level of protection against respiratory or intracerebral (i.c.) challenge. Our findings un derline the critical role of CD4(+) Th1 cells in immunity to B. pertus sis, but also demonstrate that a number of factors in the in vivo prim ing and in vitro restimulation can skew the apparent dominance of one Th cell type over another.