Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/8/2006
Publication Date: 12/3/2006
Citation: Menge, C., Stoffregen, W.C., Pohlenz, J.F., Nystrom, E.A. 2006. Dexamethasone differentially down-regulates L-Selectin (CD62L) expression by bovine lymphocyte subsets in vivo and depletes the intestinal mucosa of intraepithelial gamma delta cells [abstract]. Research Workers in Animal Diseases Conference Proceedings. p. 121.
Technical Abstract: A hallmark of immune modulation by dexamethasone (DEX) is the suppression of lymphocyte proliferation. DEX also alters the expression of adhesion molecules on bovine lymphocytes. Although intraepithelial lymphocytes (IEL) mainly are non-proliferating cells, we hypothesized that DEX treatment of cattle affects IEL by interfering with lymphocyte homing. The objectives of the present study were to investigate the effects of parenteral DEX treatment of calves (1) on the expression of CD62L - a prototype adhesion molecule - by different peripheral lymphocyte subsets and (2) on the composition of intestinal IEL. Quantitation of CD62L on peripheral lymphocytes by flow cytometry showed that DEX treatment down-regulated CD62L 48 h after the first treatment. Consistent with a principal reduction of CD62L expression on gamma delta T cells, the effect mainly pertained to CD4**- and to CD8alpha**low cells. CD8alpha**high lymphocytes were not affected. Flow cytometric analysis of IEL preparations from ileum, cecum, and distal colon 96 h after the onset of treatment showed that DEX treatment depleted intraepithelial gamma delta T cells, some of which coexpressed CD8alpha. Variable effects of DEX treatment on other subsets and expression of activation markers by gamma delta TCR**+ and CD8alpha**+ T cells were noted in ileum, colon, and cecum. Cytokine profiling (mRNA of mucosal tissue scrapings) showed that DEX treatment lowered the amounts of il-2 and il-4 but increased il-8 and ifn-gamma transcripts. Despite the variable effects of DEX treatment on IEL composition, DEX-induced changes in cytokine expression were similar throughout the intestine. This study provides the first evidence that differential effects of DEX on adhesion molecule expression by lymphocyte subpopulations alters the composition of intestinal IEL in cattle.