Brief Report: CD4+ T Cells From Patients With Systemic Lupus Erythematosus
Respond Poorly to Exogenous Interleukin-2
#MMPMID27992687
Comte D
; Karampetsou MP
; Kis-Toth K
; Yoshida N
; Bradley SJ
; Kyttaris VC
; Tsokos GC
Arthritis Rheumatol
2017[Apr]; 69
(4
): 808-813
PMID27992687
show ga
OBJECTIVE: Imbalanced cytokine production by T cells characterizes both patients
with systemic lupus erythematosus (SLE) and lupus-prone mice and contributes to
immune dysregulation. This study was undertaken to further investigate in detail
the production of interleukin-2 (IL-2), interferon-? (IFN?), IL-4, and IL-17A by
CD4+ cell subsets in healthy subjects and patients with SLE, and the signaling
response of CD4+ T cells in response to exogenous IL-2. METHODS: Cytokine
production by differentiated subsets of CD4+ T cells was assessed by
intracellular staining following stimulation with phorbol myristate acetate and
ionomycin and by enzyme-linked immunosorbent assay after anti-CD3/anti-CD28
stimulation. The IL-2 signaling pathway was examined by assessing JAK-3/STAT-5
phosphorylation. Cell proliferation in response to IL-2 was examined by
carboxyfluorescein succinimidyl ester dilution. RESULTS: Production of IL-2 was
defective primarily among naive CD4+ T cells, whereas the production of IFN?,
IL-4, and IL-17A was not significantly different between patients with SLE and
healthy subjects. JAK-3/STAT-5 phosphorylation and proliferation of CD4+ T cells
from SLE patients in response to exogenous IL-2 were impaired compared to cells
from healthy subjects. CONCLUSION: These data suggest that altered IL-2
production, as well as impaired IL-2-mediated signaling and proliferative
responses, characterize SLE CD4+ T cells. Our data demonstrate the need for
caution in designing IL-2 treatment trials for patients with SLE. Approaches to
restore CD4+ T cell sensitivity to IL-2 should be considered.
|CD4-Positive T-Lymphocytes/*immunology
[MESH]
|Cells, Cultured
[MESH]
|Humans
[MESH]
|Interferon-gamma/*biosynthesis
[MESH]
|Interleukin-17/*biosynthesis
[MESH]
|Interleukin-2/*biosynthesis/*therapeutic use
[MESH]
free
free
free
