Down-regulation of interleukin-7 receptor (CD127) in HIV infection is associated with T cell activation and is a main factor influencing restoration of CD4(+) cells after antiretroviral therapy.
BACKGROUND
Factors influencing the depletion of CD4(+) cells and the restoration of CD4(+) cells after antiretroviral therapy are not completely understood. Recently, attention has been paid to interleukin (IL)-7 and its receptor (CD127). We analyzed the influence of T cell activation and of suppression of viremia with antiretroviral therapy on this system, as well as its role in CD4(+) cell restoration after long-term antiretroviral therapy.


METHODS
IL-7 levels and CD127 expression on several subsets of CD4(+) and CD8(+) T lymphocytes and the activation status (CD38) of these cells were examined at baseline and during 24 months of complete viral suppression under highly active antiretroviral therapy (HAART).


RESULTS
A total of 42 individuals with human immunodeficiency virus (HIV) infection and 10 age-matched, uninfected control subjects were examined. Before HAART, IL-7 levels were increased and CD127 expression was decreased. Down-regulation of CD127 was mainly associated with T cell activation and reverted only partially after suppression of detectable plasma HIV RNA with HAART. In a multivariate analysis, CD127 expression on CD8(+) T cells was the main determinant of the extent of CD4(+) cell gains after successful HAART.


CONCLUSIONS
The IL-7-CD127 system is impaired in HIV-infected patients. CD127 down-regulation is associated with T cell activation and with CD4(+) cell restoration after HAART.
Benito
José M
JM
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. jbenito@hotmail.com
López
Mariola
M
Lozano
Sara
S
González-Lahoz
Juan
J
Soriano
Vincent
V
D019380:Anti-HIV Agents / Q000276:immunology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015536:Down-Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology
D019380:Anti-HIV Agents; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D012367:RNA, Viral