Memory CD4 T cell recall following Influenza A Virus infection is unaltered by the pregnancy environment

Abstract

Abstract The risk of severe influenza A virus (IAV) infection increases during pregnancy. A widely accepted paradigm suggests that this increased severity is resultant from immunity that is shifted towards Th2- versus Th1-immune responses, the latter of which is essential for control of virus. While this concept is accepted for primary immune responses, whether memory T cell responses are similarly shifted during pregnancy is unclear. Using a reductionist murine model, here we explore whether and how adoptively transferred, Th1-polarized IAV-specific memory CD4 T cells responding against IAV are impacted by pregnancy. Following infection, we find that donor cell migration to the lung, surface marker phenotype, T-BET transcription factor expression, multi-cytokine production capacity in terms of IFN-γ, TNF, and IL-2, and ability to control virus in the lung are comparable between non-gravid and gravid hosts. A significant increase in donor CD4 T cell Th2-associated GATA-3 transcription factor expression and cytokine production following IAV infection was not observed in gravid hosts. Enhancement of Th2-associated IL-4, IL-5, and IL-13 cytokine production was only observed in infected hosts when IAV-specific Th2-polarized CD4 T cells already poised to produce these cytokines were adoptively transferred. These findings suggest that in context of an IAV infection during pregnancy, preexisting Th1-polarized IAV-specific memory cells retain their protective recall potential. Furthermore, they support that employment of vaccination strategies that induce universal T cell immunity prior to pregnancy are a potential means to protect the vulnerable pregnant population from severe seasonal as well as pandemic IAV infection. The Solomon Klotz Excellence in Immunology Award Florida Education Fund McKnight Doctoral Fellowship Supported by grants from the NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) (5R21HD093948-02)