Abstract Body: Introduction: T cells play an essential role in cardiac repair after acute myocardial infarction (MI). T lymphopenia, characterized by a reduction in circulating T cells, is associated with a poor prognosis following MI. We have previously shown that MI activates the hypothalamic-pituitary-adrenal (HPA) axis to release glucocorticoids, which induce blood T-cell trafficking to the bone marrow and cause thymocyte apoptosis in the thymus, resulting in T lymphopenia. Goals: To determine whether T-cell deletion of glucocorticoid receptor (GR) would prevent T lymphopenia after MI. Methods: Adult CD4-Cre and GR^flox/flox mice were mated to generate mice with T-cell-specific deletion of GR (GR^T-KO). GR^flox/flox mice served as controls. Splenic T cells, non-T cells, and thymocytes were isolated and used to measure the expression of Nr3c1, the gene encoding GR, using real-time PCR. MI was induced by permanent ligation of the left anterior descending coronary artery. Flow cytometry was performed to quantify T cells in the blood and bone marrow and thymocytes in the thymus. Thymic weight was measured. Results: Splenic T cells and thymocytes, but not non-T cells, in GR^T-KO mice, showed a drastic decrease in Nr3c1 expression, indicating that only T cells in GR^T-KO mice were deleted of glucocorticoid receptor. At baseline, GR^T-KO and GR^flox/flox mice showed no significant difference in T-cell count in the blood and bone marrow, thymic weight, and thymocyte number. Compared with its baseline controls, GR^flox/flox mice at day 1 post-MI demonstrated T lymphopenia, T-cell accumulation in the bone marrow, smaller thymus, and less thymocytes; and these changes were not observed in day 1 post-MI GR^T-KO mice. Conclusion: Our study revealed that T-cell deletion of GR suppressed circulating T-cell trafficking to the bone marrow and thymocyte loss, thus preventing T lymphopenia after MI. Future studies will determine whether T-cell deletion of GR would improve cardiac repair and function post-MI by enhancing protective T cell response.