Abstract

CD4 T cell responses are initiated within secondary lymphoid tissue and it is within this tissue that memory CD4 T cells remain. Maintaining memory CD4 T cells is pivotal to the success of vaccination. By analysing physiological CD4 T cell responses, using a combination of MHC II tetramers and transfers of small numbers of TCR transgenic T cells, we are dissecting the signals and cells required for the generation and survival of memory CD4 T cells. Mice deficient in lymphotoxin  receptor, which lack the characteristic architecture of secondary lymphoid tissue, are unable to maintain memory CD4 T cells, indicating that cellular interactions are important for this persistence.

We have identified lymphoid tissue inducer cells, a RORgamma-dependent population responsible for the formation of lymph nodes, as key cells in sustaining memory CD4 T cells within secondary lymphoid tissue. Although primary responses appear normal in the absence of RORgamma, antigen specific memory CD4 T cells do not persist and these mice cannot mount memory antibody responses. Transfer of antigen-specific memory CD4 T cells into mice with or without lymphoid tissue inducer cells demonstrated that these cells were sufficient for maintaining memory CD4 T cells, likely through provision of OX40L signals.

We are currently further analysing the role of lymphoid tissue inducer cells within CD4 T cell responses and investigating the requirement for costimulatory molecules.