Modulation of lung environment and new T cell responses by flu‐primed CD4 memory T cells

Abstract

Infection of mice with influenza (flu) viruses generates CD4 memory T cells that reduce the accumulation of newly primed CD4 and CD8 T cells in the lungs during subsequent infections, while allowing normal T cell priming in lymphoid organs. Since the modulation of new T cell responses by CD4 memory T cells is not due to competition for antigen, we assayed for classical regulatory T cell populations within the CD4 memory T cell pool. While there was an increase in classical Treg and Tr1 phenotype T cells after flu infection, the CD4 memory T cells did not need to express CD25, GITR, or IL‐10 to carry out their modulatory functions. Gene expression in the lungs of flu infected mice adoptively transferred with CD4 memory T cells, versus naïve CD4 T cell transfer, revealed a reduced expression of genes associated with type‐1 inflammation and increased expression of genes associated with type‐2 inflammation. Thus, we are exploring whether CD4 memory T cells prevent accumulation of newly primed T cells in the lungs due to a reduced expression of type‐1 chemoattractants or active suppression of newly primed T cell survival in a type‐2 biased lung environment. However, we have not ruled out the possibility that the modulatory CD4 memory T cells may be recruiting classical regulatory T cells to the lungs during flu infection. Determining the mechanism by which CD4 memory T cells modulate newly primed T cell responses at sites of infection, and the impact this has on the generation of subsequent memory T cell responses, will yield important insights into methods for inducing protective T cell memory to a broad range of pathogens. Funding provided by NBC‐AI057158‐Lipkin.