il-15 promotes activation and expansion of cd8 t cells in ......case study: il-15 promotes...
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CASE STUDY
WHY IMMUNOSEQ?
IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection
Younes SA, et al. Journal of Clinical Immunology. 2016;126(7):2745-2756.
JULY 2016
Clonality metric allows
differentiation of antigen driven
expansion versus non-specific
bystander expansion
Enables tracking of clones between
samples and sorted subsets of cells
INFECTIOUS DISEASE
CASE STUDY: IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection— Younes SA, et al. Journal of Clinical Immunology. 2016;126(7):2745-2756.
Figure 1. Scatterplots of
clone sequences between
the cycling and non-cycling
memory CD8+ T cells in an
HIV patient and a control
show very similar overlap
patterns, indicating the cycling
population is representative
of the non cycling population,
rather than a contracted,
antigen specific subset.
Clonality metric allows
differentiation of antigen
driven expansion versus non-
specific bystander expansion
Enables tracking of clones
between samples and sorted
subsets of cells
WHY IMMUNOSEQ?BACKGROUND
Increased CD8+ T cells in circulation is linked to increased morbidity and mortality
risk in HIV-1 infected patients. HIV-1-specific expansion is present in early infection,
but the drivers for increased CD8+ T-cell numbers in chronic untreated infection is not
fully elucidated. Recent data shows that increased cycling in CD4+ T cells to be due to
bystander activation rather than antigen specific means. Here, the authors explore that
hypothesis for the CD8+ T-cell population.
AIM
• Determine if CD8+ (T-cell) cycling in untreated HIV-1 infection is antigen driven or a
bystander effect.
• Elucidate driving mechanism of CD8+ T-cell expansion in these patients.
METHODS
Sorted memory and cycling CD8+ T cells from 3 HLA-A*02:01 HIV-1 infected, untreated
patients and 3 healthy controls were sequenced.
Cycling and non cycling CD8+ T cells sorted from untreated HIV-1 infected patients
and healthy controls.
DNA extracted from sorted cells and sequenced using the human TCRB
immunoSEQ assay.
Compared clonality and sequence overlap between the two populations in each
patient or control.
RESULTS
• In both HIV-1 infected patients and controls, the cycling cell repertoires resembled the
non-cycling CD8+ memory T-cell repertoire.
• Diversity and clonality of the memory CD8+ T cells were not significantly different
between cycling and non-cycling cell subsets or between patients and controls.
• Expansion and activation of CD8+ T cells derived from the blood of healthy controls can
be induced in vitro through addition of IL-15, which is present at increased levels in lymph
nodes of untreated HIV-1 infected patients.
1
2
3
10%
10%
1%
1%
0.1%
0.1%
0.01%
0.01%
0
0
HIV patient,Non-Cycling (V-) CD8+ Clone Frequency
HIV
pati
en
t,C
ycli
ng
(V
+)
CD
8+ C
lon
e F
req
ue
ncy
10%
10%
1%
1%
0.1%
0.1%
0.01%
0.01%
0
0
Control patient,Non-cycling (C-) CD8+ Clone Frequency
Co
ntr
ol
pati
en
t,C
ycli
ng
(C
+)
CD
8+ C
lon
e F
req
ue
ncy
C1-: 12806 V1-: 9859C1+: 14010 V1+:8474Sequences in Both: 3151 Sequences in Both: 1038
CASE STUDY: IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection— Younes SA, et al. Journal of Clinical Immunology. 2016;126(7):2745-2756.
CONCLUSIONS
CD8+ T-cell activation and expansion in untreated HIV-1 infected patients is a bystander
effect and is driven by increased IL-15 expression
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