Cytokines amplify the function of accessory cells

Abstract

Accessory cells have two broad functions at the onset of T cell-mediated immunity. One is the "presentation" of antigen in association with MHC products. The other is a "sensitization" function which is thought to require IL-1 and leads to the development of lymphoblasts that secrete lymphokines and respond to T cell growth factors. This review summarizes evidence, much of it recent, that specific cytokines upregulate both the presentation and sensitization functions of accessory cells. Lymphokines, particularly IFN-gamma, upregulate class II MHC products on macrophages and many non-leukocytes, but not dendritic cells. The enhanced levels of class II improve presentation to T lymphoblasts, but not the sensitization of unprimed and memory T cells. Dendritic cells in lymph and lymphoid organs are active accessory cells for primary responses without any supplementation by exogenous cytokines. IL-1, while not a product of dendritic cells, further amplifies their function several fold. In thymus, IL-1 has a second effect, including the formation of Ia+ thymic dendritic cells from Ia- precursors. Granulocyte-macrophage colony stimulating factor (GM-CSF) is an important cytokine for epidermal Langerhans cells, which are immature dendritic cells. GM-CSF maintains viability in culture, and enhances the sensitization function for primary responses 10-20 fold. Why does the immune system regulate expression of Ia on many cell types, as well as dendritic cell function? In the discussion, it is proposed that the local modification of accessory cells by cytokines helps to reduce anti-self or autoreactive T cell responses, and to enhance the retention of sensitized T cells at sites of antigen deposition.