Cellular and Molecular Basis of Immunological Memory:
Immunological memory is the ability of lymphocytes to respond faster and more strongly to reencounter of the same antigen. It is a central feature of the adaptive immunity and is the basis of vaccination. However, little is known about the differentiation, maintenance, reactivation, and function of memory T cells. We have shown that as naïve CD8 T cells undergo proliferation in lymphopenic mice in the absence of overt antigenic stimulation, they progressively acquire phenotypic and functional characteristics of antigen-induced memory CD8 T cells. We have also developed mouse models in which CD8 T cell response to influenza virus infection can be studied at any time and in any anatomical location. By comparing the two memory T cell differentiation pathways, we have identified that TCR engagement and cell proliferation are the two requirements for memory T cell development. We are currently investigating i) genes that are required for memory CD8 T cell development and maintenance, ii) how cell proliferation (DNA replication) leads to chromatin remodeling of specific genes whose expression characterizes the memory T cell phenotype, and iii) CD8 T cell vaccines for prevention and/or treatment of virus infections in the respiratory tract.