Responsiveness of T cells to interleukin-7 is associated with higher CD4+ T cell counts in HIV-1-positive individuals with highly active antiretroviral therapy-induced viral load suppression.
BACKGROUND
Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis.


METHODS
The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects.


RESULTS
The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >or=500 CD4+ T cells/mm3>or=5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness.


CONCLUSIONS
Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.
Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78234-6200, USA.
Jose F
JF
Camargo
Hemant
H
Kulkarni
Brian K
BK
Agan
Alvaro A
AA
Gaitan
Lisa A
LA
Beachy
Sowmya
S
Srinivas
Weijing
W
He
Stephanie
S
Anderson
Vincent C
VC
Marconi
Matthew J
MJ
Dolan
Sunil K
SK
Ahuja
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D018121:Receptors, Cytokine / Q000378:metabolism; D019562:Viral Load
D019380:Anti-HIV Agents; C508605:IL7 protein, human; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D018121:Receptors, Cytokine