JOURNAL ARTICLE

IL-7-dependent STAT-5 activation and CD8+ T cell proliferation are impaired in HIV infection

Agatha Vranjkovic, Angela M Crawley, Andrea Patey, Jonathan B Angel
Journal of Leukocyte Biology 2011, 89 (4): 499-506
21177484
This study tests the hypothesis that IL-7 signaling and activity of CD8(+) T cells are impaired in HIV infection. IL-7 is necessary for optimal CTL activity and T cell survival and proliferation. Defects in IL-7R signaling may contribute to impaired activity of IL-7 observed in progressive HIV disease. A decreased proportion of CD8(+) T cells expressing the IL-7Rα chain (CD127) in progressive HIV disease would be expected to affect IL-7 activity. Alternatively, disease-associated defects of remaining CD8(+)CD127(+) T cells may influence IL-7 responsiveness. Therefore, the IL-7 responsiveness of CD8(+)CD127(+) T cells from HIV(-) and untreated or treated HIV(+) individuals was investigated. Blood was collected from HIV(-) and untreated or effectively treated HIV(+) (<50 viral copies/ml for >1 year) individuals, and CD8(+)CD127(+) T cells were isolated and cultured with IL-7. Indicators of IL-7 signaling (P-STAT5) and activity (Bcl-2 and proliferation) were evaluated by flow cytometry. Isolated CD8(+)CD127(+) T cells from untreated HIV(+) individuals expressed significantly less P-STAT5 in response to IL-7 compared with CD8(+)CD127(+) T cells from HIV(-) individuals. In effectively treated HIV(+) individuals, CD8(+)CD127(+) T cells also expressed significantly lower levels of P-STAT5 compared with HIV(-) individuals. IL-7-dependent proliferation of CD8(+)CD127(+) T cells from untreated HIV(+) individuals was similarly impaired. In contrast, IL-7-induced Bcl-2 expression was not impaired in CD8(+)CD127(+) T cells from HIV(+) individuals. These data demonstrate that IL-7/IL-7R dysfunction in HIV infection may contribute to IL-7-specific signaling defects. Decreased, IL-7-dependent activation of STAT5 and impaired proliferation may negatively impact the maintenance of CD8(+) T cell responsiveness in HIV infection.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21177484
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"