Novel IL-17–producing memory cells are key to vaccine-based protective immunity against M.tuberculosis challenge (45.12)

Abstract

Interferon-gamma (IFNγ) is essential for limiting Mycobacterium tuberculosis infection. Using the mouse model, we have recently shown that vaccination triggered accelerated Interleukin-17 (IL-17) and IFNγ responses by CD4+ T cells in the lung during M. tuberculosis aerosol challenge. We propose that vaccination induces IL-17- producing CD4+ T cells that populate the lung and, after challenge, trigger the production of chemokines. The induction of chemokines results in recruitment of IFNγ-producing CD4+ T cells from the lymphoid compartment and ultimately restricts bacterial growth. The differential ability of IL-17-producing memory cells to populate the lung compared to the IFN-γ-producing cells suggests that these two cell types differ in their ability to migrate in response to chemokines. In support of this, our data using adoptive transfer models and chemotaxis assays suggests that differential responsiveness to chemokines and retention in different organs may provide the basis for the differential tissue distribution of these two cell types. During progression from effector to memory T cells, we also show differential expression of activation markers on IL17-producing and IFNγ-producing T cells. This information will lead us to determine whether altering the nature of the lung-resident IL-17 producing population impacts protective efficacy of the recall response to M.tuberculosis challenge. This work was supported by AI075106-01 and Children's Hospital of Pittsburgh.