The broad, long term objectives for this research proposal are to understand how the innate and acquired immune systems interact in the lung during the elicitation of fibrosis and to use this knowledge in immune therapy approaches for fibrosis or other immune disorders. Hapten immune pulmonary interstitial fibrosis (HIPIF) resembles the human idiopathic pulmonary fibrosis (IPF) caused by unknown etiologies. Studies on this model could contribute to understanding the human IPF disease and lead to improved prognosis or therapy for the disease. The proposal is designed to test whether alveolar macrophages from HIPIF mice regulate (support or suppress) memory T cell responses within the lung and if mechanisms used are the same as described for macrophage regulation of primary immune responses.
Aim 1 HIPIF- generated and control macrophages will be tested for regulation of in-vitro antigen mediated T cell proliferation and activation.
Aim 2 will determine if alveolar macrophage regulation of secondary T cell responses is mediated by soluble factors such as (TNFalpha, IL12 or TGFbeta) by using blocking antibodies in-vitro and in-vivo.
Aim 3 will look at the role of co-stimulatory molecules (B7, CD40) in the hapten induction of the secondary response by using blocking reagents and genetically altered mice. Data generated from this proposal will provide novel information concerning macrophage regulation in the secondary immune responses.
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