TY - JOUR

T1 - Reduced IL-7R T Cell Expression and Increased Plasma sCD127 in Late Presenting HIV-Infected Individuals

AU - Hartling, Hans J

AU - Jespersen, Sofie

AU - Gaardbo, Julie C

AU - Sambleben, Camilla

AU - Thorsteinsson, Kristina

AU - Gerstoft, Jan

AU - Ullum, Henrik

AU - Nielsen, Susanne D

PY - 2017/1/1

Y1 - 2017/1/1

N2 - BACKGROUND: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART.METHODS: A total of 100 HIV-infected individuals initiating cART were included in a prospective study. Samples were collected at baseline and after 6, 12, and 24 months of cART. Proportion and expression {[median fluorescence intensity (MFI)]} of IL-7R on T cells, and plasma concentrations of soluble CD127 (sCD127) and IL-7 were determined.RESULTS: The IL-7R expression was reduced in late presenters with CD4 cell count <200 cells per microliter compared with nonlate presenters and healthy controls as demonstrated by lower proportion of CD127 + CD132 + T cells and lower CD127 MFI. In contrast, plasma sCD127 was higher. These differences were partly reversed after suppressive cART. Interestingly, the CD127 MFI on CD4 T cells was found to be a predictor of increased thymic output after 24 months of suppressive cART.CONCLUSIONS: Severely altered IL-7R expression was found in late presenters, and associations between IL-7R expression and thymic output after 24 months of suppressive cART indicate an impact of a IL-7 response for the long term de novo production from thymus.

AB - BACKGROUND: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART.METHODS: A total of 100 HIV-infected individuals initiating cART were included in a prospective study. Samples were collected at baseline and after 6, 12, and 24 months of cART. Proportion and expression {[median fluorescence intensity (MFI)]} of IL-7R on T cells, and plasma concentrations of soluble CD127 (sCD127) and IL-7 were determined.RESULTS: The IL-7R expression was reduced in late presenters with CD4 cell count <200 cells per microliter compared with nonlate presenters and healthy controls as demonstrated by lower proportion of CD127 + CD132 + T cells and lower CD127 MFI. In contrast, plasma sCD127 was higher. These differences were partly reversed after suppressive cART. Interestingly, the CD127 MFI on CD4 T cells was found to be a predictor of increased thymic output after 24 months of suppressive cART.CONCLUSIONS: Severely altered IL-7R expression was found in late presenters, and associations between IL-7R expression and thymic output after 24 months of suppressive cART indicate an impact of a IL-7 response for the long term de novo production from thymus.

KW - Journal Article

U2 - 10.1097/QAI.0000000000001153

DO - 10.1097/QAI.0000000000001153

M3 - Journal article

C2 - 27509242

VL - 74

SP - 81

EP - 90

JO - J A I D S

JF - J A I D S

SN - 1525-4135

IS - 1

ER -