Publications

BACKGROUND

The cell adhesion molecule integrin alpha 4 beta 7 helps direct the migration of blood lymphocytes to the intestine and associated lymphoid tissues. We hypothesized that beta 7+ and beta 7- blood memory T helper cells differ in their expression of genes that play a role in the adhesion or migration of T cells.

RESULTS

RNA was prepared from beta 7+ and beta 7- CD4+ CD45RA- blood T cells from nine normal human subjects and analyzed using oligonucleotide microarrays. Of 21357 genes represented on the arrays, 16 were more highly expressed in beta 7+ cells and 18 were more highly expressed in beta 7- cells (>/=1.5 fold difference and adjusted P < 0.05). Several of the differentially expressed transcripts encode proteins with established or putative roles in lymphocyte adhesion and chemotaxis, including the chemokine receptors CCR9 and CCR10, the integrin alpha 4 subunit, L-selectin, KLRB1 (CD161), NT5E (CD73), LGALS1 and LGALS2 (galectin-1 and -2), and RGS1. Flow cytometry was used to determine whether differences in levels of transcripts encoding cell surface proteins were associated with differential expression of those proteins. Using this approach, we found that surface expression of KLRB1, LAIR1, and NT5E proteins was higher on beta 7+ memory/effector T cells than on beta 7- cells.

CONCLUSIONS

Memory/effector T cells that express integrin beta 7 have a distinct pattern of expression of a set of gene transcripts. Several of these molecules can affect cell adhesion or chemotaxis and are therefore likely to modulate the complex multistep process that regulates trafficking of CD4+ memory T cell subsets with different homing behaviors.

In 2003 citizens of Canada, the United Kingdom, and France paid an average of 34-59 percent of what Americans paid for a similar market basket of pharmaceuticals. If the Medicare program were to pay comparable prices for pharmaceuticals, it would be possible to eliminate the "doughnut hole" in its prescription drug benefit and keep Medicare drug spending within the overall limits established by Congress. This provides Congress with a clear choice: reduce the level of cost sharing and improve beneficiaries' access to pharmaceuticals, or allow the pharmaceutical industry to use the higher prices to fund research and development and to engage in other activities.

To examine the association between depressive symptoms and exercise capacity, we performed a cross-sectional study of 944 outpatients with stable coronary artery disease and found that the presence of depressive symptoms was independently associated with poor exercise capacity (<5 MET tasks achieved; adjusted odds ratio 1.8, 95% confidence interval 1.1 to 2.7, p = 0.01). Depressive symptoms should be considered in the differential diagnosis of poor exercise capacity.