Altered Responses to Homeostatic Cytokines in Patients with Idiopathic CD4 Lymphocytopenia

作者：Bugault Florence; Benati Daniela; Mouthon Luc; Landires Ivan; Rohrlich Pierre; Pestre Vincent; Theze Jacques; Lortholary Olivier; Chakrabarti Lisa A^*

来源：PLos One, 2013, 8(1): e55570.

DOI：10.1371/journal.pone.0055570

Idiopathic CD4 lymphocytopenia (ICL) is a rare immune deficiency characterized by a protracted CD4(+) T cell loss of unknown etiology and by the occurrence of opportunistic infections similar to those seen in AIDS. We investigated whether a defect in responses to cytokines that control CD4(+) T cell homeostasis could play a role in ICL. Immunophenotype and signaling responses to interleukin-7 (IL-7), IL-2, and thymic stromal lymphopoietin (TSLP) were analyzed by flow cytometry in CD4(+) T cells from 15 ICL patients and 15 healthy blood donors. The induction of phospho-STAT5 after IL-7 stimulation was decreased in memory CD4(+) T cells of some ICL patients, which correlated with a decreased expression of the IL-7R alpha receptor chain (R = 0.74, p%26lt;0.005) and with lower CD4(+) T cell counts (R = 0.69, p%26lt;0.005). IL-2 responses were also impaired, both in the Treg and conventional memory subsets. Decreased IL-2 responses correlated with decreased IL-7 responses (R = 0.75, p%26lt;0.005), pointing to combined defects that may significantly perturb CD4(+) T cell homeostasis in a subset of ICL patients. Unexpectedly, responses to the IL-7-related cytokine TSLP were increased in ICL patients, while they remained barely detectable in healthy controls. TSLP responses correlated inversely with IL-7 responses (R = 20.41; p%26lt;0.05), suggesting a cross-regulation between the two cytokine systems. In conclusion, IL-7 and IL-2 signaling are impaired in ICL, which may account for the loss of CD4(+) T cell homeostasis. Increased TSLP responses point to a compensatory homeostatic mechanism that may mitigate defects in gamma c cytokine responses.

• 出版日期2013-1-30