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HIV1 infection decreases CD127

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Title: HIV1 infection decreases CD127


1
  • HIV-1 infection decreases CD127
  • and PD1 expression on duodenal
  • CD8T cells
  • Liliana Belmonte, PhD
  • Academia Nacional de Medicina
  • Buenos Aires, Argentina

2
Background
  • The GI tract is a major site of HIV
    replication and pathogenesis, regardless of the
    specific tissue site of viral entry.
  • Persistence of HIV in the duodenal mucosa
    even when effective therapy suppresses HIV-RNA in
    blood to undetectable levels, has been
    demonstrated by previous studies from our group.
  • (Belmonte L et al, AIDS 200721(15)2106-8).

3
Chronic HIV infection often results in
ineffective CD8 T-cell responses. However the
mechanisms triggered by persisting virus
infection and their impact on CD8 T-cell effector
functions and tissue distribution, remain
unknown.
  • Specific Aim
  • To analyse the quality of duodenal CD8 T cells
    in chronically HIV-infected patients.

4
Distal Duodenal biopsies
26 patients with chronic HIV-1 infection under
HAART
13 HIV-1 seronegative individuals were included
as control (C)
  • We analyzed the presence of HIV-DNA in the
    duodenal tissue. A biopsy was labeled as HIV
    if HIV-DNA was detected by standard PCR
  • (using the primers SK145 and SKCC1B to define
  • a sequence of 155 nucleotides within the highly
    conserved region of the HIV-1 gag gene)

5
Distal Duodenal biopsies
26 patients with chronic HIV-1 infection under
HAART
13 HIV-1 seronegative individuals were included
as control (C)
  • Endoscopic material were disrupted mechanically
    and a cell suspension was prepared. Expression
    of CD4, CD8, CD27, CD28, CD45RO, CD45RA, CCR7,
    CD127, PD-1 (BD) was analysed by flow cytometry
    (FacScan, BD).
  • We analyzed the presence of HIV-DNA in the
    duodenal tissue. A biopsy was labeled as HIV
    if HIV-DNA was detected by standard PCR
  • (using the primers SK145 and SKCC1B to define
  • a sequence of 155 nucleotides within the highly
    conserved region of the HIV-1 gag gene)

6
Percentages of CD4 and CD8 T cells in the
duodenal mucosa
7
Duodenal Memory CD8 T cell differentiation
(CD45RA, CCR7 expression)
Terminally differentiated cells
Pre-terminally differentiated cells
Precursor memory T cells
8
Duodenal Memory CD8 T cell differentiation
(CD27, CD28 expression)
CD8 CD28 CD27
Early Differentiated cells
CD8 CD28- CD27
Intermediate Differentiated cells
Late effector cells
CD8 CD28- CD27-
9
High Programmed-death 1 (PD-1) expression on
duodenal CD8 T cells from HIV patients
pns
HIV biopsies
HIV- biopsies
Controls
10
Decreased CD127 high (IL7R) expression on
duodenal CD8 T cells from HIV patients
pns
HIV biopsies
HIV- biopsies
Controls
11
Conclusions
  • Our results demonstrate an accumulation of the
    pre-terminally differentiated subset of memory
    cells. This findings could be due to a depletion
    of terminally differentiated CD8 T cells and/or
    lack of CD4 helper activity.

12
Conclusions
  • Our results demonstrate an accumulation of the
    pre-terminally differentiated subset of memory
    cells. This findings could be due to a depletion
    of terminally differentiated CD8 T cells and/or
    lack of CD4 helper activity.
  • The pool of late effector CD8 T cells (CD27-,
    CD28-) was higher in HIV patients than in C.
    However, in HIV patients with HIV biopsies this
    value was lower than in those with HIV- biopsies,
    suggesting that continuous Ag exposure leads to
    late effector cell loss.

13
Conclusions
  • PD-1 was significantly up-regulated on duodenal
    CD8 T cells in HIV patients. Functional
    impairment (exhaustion) could lead to ineffective
    viral control, since in the biopsies where HIV
    persisted, the of exhausted cells tended to be
    higher.

14
Conclusions
  • PD-1 was significantly up-regulated on duodenal
    CD8 T cells in HIV patients. Functional
    impairment (exhaustion) could lead to ineffective
    viral control, since in the biopsies where HIV
    persisted, the of exhausted cells tended to be
    higher.
  • HIV infection suppressed CD127high expression
    on duodenal CD8 T lymphocytes. The proportion of
    CD127-expressing cells was slightly lower in the
    biopsies where HIV persisted and this could be
    related to T cell exhaustion. These data support
    further the concept that HIV infection can alter
    memory CD8 differentiation.

15
Aknowledgements
  • Gastroenterology Unit- City Hospital Juan A
    Fernandez
  • Alberto Zalar, MD
  • Norma Correa, MD
  • Infectious Diseases Unit-City Hospital Juan A
    Fernandez
  • Pedro Cahn, MD, PhD
  • Maria Inés Figueroa, MD
  • Laboratory of Immunology- Academia Nacional de
    Medicina
  • Ana Coraglia, PhD st
  • Maria Marta de E de Bracco, PhD
  • ANPCyT-MinCyT and Roemmers Foundation for
    financial support
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