Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2002
Publication Date: 1/1/2003
Citation: Waters, W.R., Palmer, M.V., Cheng, D., Nonnecke, B.J., Whipple, D.L. 2003. Expression of l-selectin (cd62l), cd44, and cd25 on activated bovine t cells. Infection and Immunity.
Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, a recent outbreak of tuberculosis in white-tailed deer in Michigan has seriously hindered eradication efforts within the United States. Improved techniques are needed for detection of infected cattle. To develop improved diagnostics, it is beneficial to understand the immune response of cattle to tuberculosis infection. In this study, it was determined that stimulation of immune cells from tuberculosis-infected cattle results in specific changes in surface parameters of these cells. Knowledge obtained from this study will assist in the development of new reagents and methods for the detection of tuberculosis of cattle.
Technical Abstract: Mycobacterium bovis infection of cattle represents a natural host/pathogen interaction and, in addition to its economic and zoonotic impact, represents a model for human tuberculosis. Extravasation and trafficking of activated lymphocytes to inflammatory sites is modulated by differential expression of multiple surface adhesion molecules. However, effects of M. bovis infection on adhesion molecule expression are not characterized. To determine these changes, peripheral blood mononuclear cells (PBMC) from M. bovis-infected cattle were stimulated with M. bovis purified protein derivative (PPD) or pokeweed mitogen (PWM) and evaluated concurrently for proliferation and activation marker expression. Stimulation with PPD or PWM increased CD25 and CD44 mean fluorescence intensity (mfi) and decreased CD62L mfi on CD4+ cells from infected animals. CD62L mfi on PPD- and PWM-stimulated gammadelta TCR+ and CD8+ cells was also reduced when compared to that of non-stimulated gammadelta TCR+ and CD8+ cells. Using a flow cytometric-based proliferation assay, it was determined that proliferating cells, regardless of lymphocyte subset, exhibited increased expression of CD25 and CD44 and decreased expression of CD62L when compared to that of cells that had not proliferated. In contrast to proliferation, activation-induced apoptosis of CD4+ cells resulted in a significant down regulation of CD44 expression. Lymphocytes obtained from lungs of M. bovis-infected cattle also had reduced expression of CD44 when compared to lymphocytes from lungs of non-infected cattle. These alterations in surface molecule expression upon activation likely impact trafficking to sites of inflammation and the functional capacity of these cells within tuberculous granulomas.