T cell alterations in a mouse model of neglect-related early life stress




Choe, Jamie Y.
Donkor, Michael
Jones, Harlan P.


0000-0002-5488-0328 (Donkor, Michael)

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Exposure to severe or chronically stressful life events during childhood—referred to as early life stress (ELS)—is associated with negative effects on health across the life course. Neglect is a significant source of ELS during childhood and accounts for over 75% of maltreatment-related child abuse in the United States. Animal models of ELS emulate the nature of childhood neglect through scheduled separation. A major challenge in studying the impact of stress on immune competency has been the difficulty of developing a reliable mouse model. The thymus is responsible for producing self-tolerant T cells and is critical for adaptive immunity. Developing T cells can be identified based on CD4/CD8 expression status which corresponds to defined stages in thymocyte maturation. We developed a novel murine model of neglect-related ELS based on the maternal separation with early weaning (MSEW) paradigm featuring scheduled dam-pup separation and early weaning to a high carbohydrate diet. This study investigates the effect of ELS on surface markers for thymic T cell development and distribution. Pups were produced by in-house breeding and subjected to one of two distinct ELS conditions: (1) daily dam-pup separation with early weaning (MSEW) or (2) the early weaning condition alone (EW) at postnatal day (PD) 14. Control pups were maintained on the dam’s milk to the standard wean date (PD21). Tissues were collected at PD21 after euthanasia. Flow cytometry revealed significant differences in the distribution of PD21 thymocytes between the double-positive CD4+CD8+ (DP) and single-positive (SP) compartments. Our data indicate that neglect-related ELS can disrupt the baseline distribution of developing T cells within defined thymic compartments and suggests ELS exposure may have downstream ramifications on T cell immunity.