Nematode infection enhances survival of activated T cells by modulating accessory cell function

The type of immune response generated following exposure to Ag depends on a variety of factors, including the nature of the Ag, the type of adjuvant u sed, the site of antigenic entry, and the immune status of the host. We hav e previously shown that infection of rodents with Nippostrongylus brasilien sis (Nb) shifts the development of type 1 allo-specific responses toward ty pe 2 immunity; suggesting nematode modulation of T cell activation, In this report we explore the immunomodulatory effects of Nb on T cell activation. We found that spleen cells from Nb-infected mice exhibited dramatically in creased proliferation in; response to Con-A and anti-CD3. This hyperprolife ration could be transferred in vitro to naive splenocytes by coculture with mitomycin C-treated cells from,Vb-infected animals. The transfer was media ted by non-T accessory cells and supernatants derived from Con A-activated non-T cells, suggesting the involvement of a soluble factor secreted by acc essory cells. The accessory cells secreted high levels of IL-6, and anti IL -6 treatment abrogated the supernatant-induced hyperproliferation, thus con firming that IL-6 was mediating the effect. Further, spleen cells from Nb-i nfected mice were more resistant to activation-induced cell death (AICD) fo llowing mitogenic stimulation. Reduced AICD was also transferable and IL-6 dependent. Thus, the hyperproliferation was in part due to enhanced activat ed T cell survival. These phenomena mediated by accessory cells may contrib ute to the powerful polyclonal activation of type 2 immunity caused by nema tode infection.