Skin-resident T cells: the ups and downs of on site immunity

Abstract

The cutaneous surface of a normal adult individual contains approximately 20 billion T cells, nearly twice the number present in the entire circulation. Recent studies have shown a role for these cells in both normal immunity and in inflammatory skin diseases such as psoriasis. Regulatory T cells protect against autoimmune reactions to self antigens and assist in the resolution of cutaneous inflammation. However, they can also shield tumors from immune detection, allow latent infections to persist and can dysfunction under the conditions present in inflammatory skin diseases. Th17 T cells protect organisms against extracellular pathogens but also have a key role in the pathogenesis of psoriasis. Evidence suggests that effector memory T cells produced during immune reactions survive and persist long term within the skin, providing local and rapid protection against pathogen reexposure. This review summarizes the current understanding of how skin-resident T cells contribute to normal and aberrant immunity in the skin.

Figure 1. Contributions of T_EM and T_CM to primary immune responses in the skin

After pathogen exposure, DC take up antigen, migrate to the skin draining lymph nodes and present it to naïve T cells. Naïve T cells that recognize their cognate antigen undergo differentiation and polarization in to skin homing effector memory T cells (T_EM) and central memory T cells (T_CM). T_EM leave the lymph nodes, enter the circulation and migrate into the skin where they effect clearance of the pathogen. T_EM colonize all areas of the skin but are found in highest numbers at sites of pathogen exposure. In the early stages of the immune response, proliferating T cells are also released from the skin draining lymph nodes and migrate to antigen-free lymph nodes draining other peripheral tissues. T cells continue to proliferate within these lymph nodes, giving rise to new populations of T_EM that home to gut, lungs and other peripheral tissues. In this way, immunization through the skin gives rise to a diverse population of tissue resident T cells that provide systemic immune protection.

Figure 2. The role of T_EM and T_CM in recall immune responses

Memory immune responses can be divided into three stages. First, DC take up antigen following pathogen re-exposure and present it to T_EM resident locally within the skin. These cells proliferate and effect clearance of the pathogen. Second, inflammation leads to endothelial activation and nonspecific recruitment of T cells from the blood. The small numbers of antigen-specific T cells recruited into the skin in this way can also participate in clearance of the pathogen. Third, DC carry endocytosed antigen to the skin draining lymph nodes where it is presented to T_CM. These T_CM then give rise to new populations of skin homing T_EM that migrate to the skin and clear the infection.