T-Cell Induced Colitis Is Associated With Enhanced Myelopoiesis, PMN Infiltration into Secondary Lymphoid Tissue and Modulation of T-Cell Activation (98.6)

Abstract

Abstract The objective of this study was to determine how the adoptive transfer of naïve T-cells into lymphopenic recipients affects myelopoiesis during the development of chronic colitis. We found that adoptive transfer of CD4+CD45RBhigh T-cells (5x105 cells) into RAG-1−/− recipients induced chronic colitis that was preceded by a dramatic leukocytosis/myelopoiesis in which total circulating leukocytes increased 5–6 fold compared to unmanipulated RAG-1−/− mice with PMNs representing >85% of the total blood leukocytes. In addition, we found that serum levels of the granulopoietic cytokines IL-17 and G-CSF increased by 4- and 9-fold, respectively compared to the healthy CD45RBlow→RAG-1−/− controls. Corresponding to these dramatic increases in systemic PMN production in the CD45RBhigh→ RAG-1−/− mice, were large and significant increases (30–50-fold) in the presence of granulocytes (Gr-1+/Mac-1+) in the spleen, MLNs and colonic lamina propria. Co-culture of irradiated leukocytes (5 x 103 cells) obtained from the MLNs or spleen (>60% PMNs) of colitic mice with CD4+ T-cells (105 cells) enhanced CD/CD28-induced T-cell proliferation by 2–3 fold. We conclude that the T-cell induced myelopoiesis and infiltration of PMNs into the secondary lymphoid tissue of lymphopenic recipients may enhance T-cell activation thereby modulating the onset and/or severity of colonic inflammation (Supported DK64023).