Alpha E Beta 7, Alpha 4 Beta 7 And Alpha 4 Beta 1 Integrin Contributions To T Cell Distribution In Blood, Cervix And Rectal Tissues: Potential Implications For Hiv Transmission

Cell surface expression of alpha 4 beta 7, alpha 4 beta 1 and alpha E beta 7 integrins play a key role in T cell distribution. Understanding the contribution of integrins to the density and ratios of CD4(+):CD4(neg)T cell at the portals of entry for HIV is of fundamental importance for the advance of more effective HIV prevention strategies. We therefore set out to characterize and compare the expression of alpha 4 beta 7, alpha 4 beta 1 and alpha E beta 7 integrins on systemic, cervical and rectal CD4(+) and CD4(neg) T cells isolated from a cohort of healthy Kenyan women at low risk for sexually transmitted infections (STI) (n = 45). Here we show that blood and cervix were enriched in alpha 4(+)beta 1(+)CD4(+)T cells and alpha 4(+)beta 7(hi)CD4(+)T cells, whereas the rectum had an equal frequency of alpha 4(+)beta 7(hi)CD4(+)T cells and alpha E+ss 7(hi)CD4(+)T cells. Most cervical and rectal alpha E+beta 7(hi) CD4(+)T cells expressed CCR5 as well as CD69. Interestingly, alpha E beta 7 was the predominant integrin expressed by CD4(neg)T cells in both mucosal sites, outnumbering alpha E+beta 7(hi) CD4(+)T cells approximately 2-fold in the cervix and 7-fold in the rectum. The majority of alpha E+beta 7(hi) CD4(neg)T cells expressed CD69 at the mucosa. Taken together, our results show unique tissue-specific patterns of integrin expression. These results can help in guiding vaccine design and also the use of therapeutically targeting integrin adhesion as a means to preventing HIV.