There was no association detected between activation markers and the GLUT 1 glucose transporter. The major finding of the current study relates to ADA, which when complexed to CD26 on antigen-presenting cells, constitutes a key coLuciferase does not undergo the significant post-translational modification within the ER that envelope glycoproteins stimulatory component of the immunological synapse. Our analysis provides the first demonstration 
that ADA is significantly reduced in CD8+ T cells from those HIV-1-infected individuals with high CD38 expression, a biomarker of immune activation. This observation is consistent with extensive data on loss of ADA expression caused by chronic activation of CD8+ T cells in cell culture. Using regression analysis, ADA positivity was also found to serve as the strongest variable among our biomarkers that accounts for more than half of variation of expression of CD38+HLA-DR+, markers frequently used in clinical settings to evaluate HIV disease progression. In addition, since ADA is essential for optimal telomerase activity in CD8+ T lymphocytes, the results of this study, indicating the inverse relationship between CD38 and T cell telomerase activity, may support the upstream stimulatory function of ADA on telomerase activity. This observation has important in vivo consequences, since T cells lacking ADA are vulnerable to adenosine, an immunosuppressive factor produced by certain Tregs and present in the microenvironment of many tumors. Moreover, exposure of CD8+ T cells to adenosine in cell culture accelerates many of the changes associated with senescence, such as reduced proliferative potential, diminished IL-2 message, and early loss of both CD28 expression and telomerase activity. Our study also demonstrates strong associations between telomerase activity, LRRN3 gene expression and CD38 levels, and may therefore establish a novel panel of parameters that can be used in future clinical evaluation of our hypothesis. Together, the data provide a more definitive picture of the dysfunctional CD8+ T cell compartment in HIV-infected persons. Indeed, further refining of the genetic and molecular signature of senescent CD8+ T cells in the HIV-1-infected population may be beneficial in assisting clinicians to strategize the course and intensity of ART treatment for individual patients. Interestingly, although GLUT 1 expression and glucose uptake in T cells are both modulated by CD28, our analysis failed to show any association between GLUT 1 expression and CD8+ T cell activation. The accumulation of senescent CD8+ T cells affects not only immune function, but may also impact other physiological systems. Indeed, a recent study by Kaplan et al. showed that frequencies of both highly activated and senescent T cells in HIV-1infected women were associated with increased prevalence of carotid artery lesions. It was concluded that HIV-associated T cell changes, characterized by specific senescence and activation markers, are associated with subclinical carotid artery abnormalities, which are observed even among those patients achieving viral suppression with effective ART.