Details

Autor(en) / Beteiligte

• Fry, Terry J.
• Connick, Elizabeth
• Falloon, Judith
• Lederman, Michael M.
• Liewehr, David J.
• Spritzler, John
• Steinberg, Seth M.
• Wood, Lauren V.
• Yarchoan, Robert
• Zuckerman, Judy
• Landay, Alan
• Mackall, Crystal L.

Titel

A potential role for interleukin-7 in T-cell homeostasis

Ist Teil von

• Blood, 2001-05, Vol.97 (10), p.2983-2990

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• Interleukin (IL)-7 is known to up-regulate thymopoietic pathways of T-cell regeneration. Recent work also has shown it to potently enhance thymic-independent peripheral expansion and to restore immunocompetence in athymic T-cell–depleted hosts. We hypothesized that endogenous IL-7 could contribute to the restoration of T-cell homeostasis following T-cell depletion. To analyze this, we evaluated circulating IL-7 levels and lymphocyte subsets in multiple clinical cohorts with T-cell depletion of varying etiologies. In pediatric (n = 41) and adult (n = 51) human immunodeficiency virus–infected CD4-depleted patients, there were strong inverse correlations between IL-7 levels and CD4 counts (r = −0.77, P < .0001, andr = −0.68, P < .0001). Declines in IL-7 were temporally correlated with recovery of CD4 counts. Similar patterns were observed in CD4-depleted patients receiving cancer chemotherapy (r = −0.65, P = .009). Therefore, in 2 disparate clinical scenarios involving CD4 depletion, IL-7 levels dynamically respond to changes in CD4 T-cell number, making this cytokine uniquely suited as a candidate regulator of T-cell homeostasis. Furthermore, in patients with idiopathic CD4 lymphopenia, a much weaker relationship between IL-7 levels and peripheral blood CD4 counts was observed, suggesting that an impaired IL-7 response to CD4 depletion may contribute to the impaired lymphocyte homeostasis observed in this population. In light of the known effects of IL-7 on T-cell regeneration, we postulate that increased availability of IL-7 could play a critical role in restoring T-cell homeostasis following T-cell depletion.