Th2 Responses to Inactivated Influenza Virus Can Be Converted to Th1 Responses and Facilitate Recovery from Heterosubtypic Virus Infection

Immunization with live influenza virus expands Th memory cells and facilitates more rapid recovery after heterosubtypic virus challenge. Immunization with inactivated virus generates a Th2 response and does not lead to heterosubtypic immunity. Creation of a Thl priming environment by the inclusion of interleukin (IL)-12 with antibodies to IL-4 converted the response against inactivated virus to a Thl response that was able to facilitate virus clearance upon heterosubtypic virus challenge. Evaluation of memory responses of mice immunized by the various protocols demonstrated that the type of immunization imprints T cell memory, dictating the nature of the response to subsequent infection. After live virus challenge, expansion of Thl cells seems to facilitate the generation of cytotoxic T lymphocytes from naive precursors. This latter finding may be the mechanism by which inactivated virus immunization in a Thl cytokine context mediates heterosubtypic immunity.