HIV-infected patients, and have proliferative defects

Slides:

Advertisements

Similar presentations

High Affinity HIV-1 Specific CTL Become Exhausted in Early HIV-1 Infection High Affinity HIV-1 Specific CTL Become Exhausted in Early HIV-1 Infection Abstract.

Advertisements

Treg exert differential effects on the proliferation and differentiation of CD8 T cell subsets in chronic HIV-1 infection M. Nikolova 1, M. Muhtarova 1,

Detection of Immune Responses in Mucosal T-cells in Kenya Jackton Indangasi 2, Hannah Cheeseman 1, Onyango J. I. Obila 2, Simon Ogola 2, Robert Langat.

HIV-1 infection decreases CD127 and PD1 expression on duodenal CD8+T cells Liliana Belmonte, PhD Academia Nacional de Medicina Buenos Aires, Argentina.

Laser Flow Cytometry Forward Scatter indicates size Forward Scatter.

HIV pathogenesis The course of HIV infection 1. Acute Phase 2. Intermediate (asymptomatic) phase -viral load stabilizes at a “set point”. 3. Late (symptomatic)

Background  HIV-1 infection persists in reservoirs and leads to progressive depletion of CD4+ T-cells even in subjects with slow disease progression 

Expression Analysis of α4 integrin and related genetic polymorphisms in HIV acquisition and disease progression OF infected individuals Livia R. GóeS 1,

coinciding with biphasic immune reconstitution

a b c Figure S1 Figure S1: Gating strategy describing T cell subsets.

A. B. EXP #1: 3 donors EXP #2: 3 donors EXP #3: 6 donors EXP #4:

Chronic immune activation in HIV associated Non Hodgkin lymphoma and the effect of antiretroviral therapy Brian Flepisi University of the Western Cape.

Cytokine Production and Antigen Recognition by Human Mucosal Homing Conjunctival Effector Memory CD8+ T Cells Invest. Ophthalmol. Vis. Sci ;55(12):

FREQUENCIES AND PHENOTYPIC CHANGES OF DENDRITIC CELLS DURING ACUTE DENGUE VIRAL INFECTION Lertjuthaporn S1, Khowawisetsut L2, Keawvichit R1, Thitilertdecha.

Volume 66, Issue 6, Pages (June 2013)

Figure 2 Percentage of CD19+/CD34+ cells with decreased CD81 median fluorescence intensity (MFI;

Dominant IL-21 expression in TFH cells correlate with B cell pathology in HIV-infected LNs. Dominant IL-21 expression in TFH cells correlate with B cell.

Foxp3 induction dependent on cell cycle progression in vitro.

“Analyses of Pre-therapy Peripheral Immunoscore and Response to

Supplementary Figure 2 Supplementary Figure 2. White blood cell differential count White blood cell (WBC) differential counts were analyzed from patients.

Coinfection With HIV-1 and HCV—A One-Two Punch

Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection

T cell mediated immunity

CD158k Is a Reliable Marker for Diagnosis of Sézary Syndrome and Reveals an Unprecedented Heterogeneity of Circulating Malignant Cells Hélène Moins-Teisserenc,

Impaired function of human T-lymphotropic virus type 1 (HTLV-1)–specific CD8+ T cells in HTLV-1–associated neurologic disease by Amir H. Sabouri, Koichiro.

by Jason M. Brenchley, Mirko Paiardini, Kenneth S. Knox, Ava I

Altered Homeostasis of CD4+ Memory T Cells in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Chronic Graft-versus-Host Disease Enhances T Cell.

Maraviroc contributes to the restoration of the homeostasis of regulatory T-cell subsets in antiretroviral-naive HIV-infected subjects M.M. Pozo-Balado,

Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment.

FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV-1 infection by Timothy J. Wilson, Rachel M. Presti,

by Vladia Monsurrò, Ena Wang, Yoshisha Yamano, Stephen A

Volume 147, Issue 1, Pages e7 (July 2014)

Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before.

Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD by Joanne E. Croudace, Charlotte F.

Jason M. Brenchley, Guido Silvestri, Daniel C. Douek Immunity

Hepatitis C and Lymphoproliferative Disorders: From Mixed Cryoglobulinemia to Non- Hodgkin's Lymphoma Lenna A. Martyak, Melina Yeganeh, Sammy Saab Clinical.

Role of monocytes in NK cell activity.

Volume 153, Issue 5, Pages e2 (November 2017)

Course of disease and immune responses seen in patient LAU 672.

Volume 21, Issue 12, Pages (December 2017)

Flow cytometric analysis of putative progenitor cells.

Successful and Maladaptive T Cell Aging

Volume 15, Issue 4, Pages (October 2001)

Volume 35, Issue 5, Pages (November 2011)

Tetramer staining performed to determine frequencies of epitope-specific T cells after clearance of HPV16 infection but prior to isolation of T-cell clones.

Figure 1 Schematic overview of flow cytometry Schematic overview on the analysis of peripheral immune cells by flow cytometry. Schematic overview of flow.

Volume 38, Issue 1, Pages (January 2013)

Fig. 1 Effect of preinfection β7Hi CD45RA−CD4+ T cell frequency on HIV acquisition risk in CAPRISA 004 study. Effect of preinfection β7Hi CD45RA−CD4+ T.

Phenotype of rTT.C-specific plasma blasts.

Volume 123, Issue 4, Pages (October 2002)

Recasting Human Vδ1 Lymphocytes in an Adaptive Role

Fig. 1. Exposure to P. duboscqi uninfected sand flies (USFs) induces an anti-saliva immunity that protects NHP from vector-transmitted CL. Exposure to.

Volume 21, Issue 6, Pages (December 2004)

Fig. 2 CD32+ cells have a distinctively different phenotype compared to CD32− cells. CD32+ cells have a distinctively different phenotype compared to CD32−

Theoretical Immunology: Aging

Figure 1 BG-12 treatment reduced total circulating B cells and had variable effects on memory B cells BG-12 treatment reduced total circulating B cells.

Donor and recipient BAL T cells are phenotypically and functionally memory T cells. Donor and recipient BAL T cells are phenotypically and functionally.

CD27 expression on bovine γδ and CD4 T cells ex vivo and in response to mitogen. CD27 expression on bovine γδ and CD4 T cells ex vivo and in response to.

The gastrointestinal tract is critical to the pathogenesis of acute HIV-1 infection Saurabh Mehandru, MD, Klara Tenner-Racz, MD, Paul Racz, MD, PhD, Martin.

Volume 15, Issue 4, Pages (October 2001)

MK-8628 suppresses T lymphocyte proliferation.

by Zaza M. Ndhlovu, Samuel W

Blood Tfr cells are immature but are not committed in the thymus.

HBeAg seroconversion is associated with a more effective PD-L1 blockade during chronic hepatitis B infection Sara Ferrando-Martinez, Kelly Huang, Angie.

Share your thoughts on this presentation with #IAS2019

IL-9–expressing TH cells are highly enriched in CCR4+/CCR8+ effector memory TH cells. IL-9–expressing THcells are highly enriched in CCR4+/CCR8+effector.

Memory phenotypes PBMC-derived MERS-CoV-specific T cells from CWs

Volume 20, Issue 6, Pages (June 2004)

Figure 4 Longitudinal analysis of peripheral immune cell composition Frequency of naive, central memory (Tcm), and effector memory (Tem) CD4 T cells over.

Presentation transcript:

HIV-infected patients, and have proliferative defects Activated Th1 and Th2-committed central memory CD4+ T Cells are over-represented in HIV-infected patients, and have proliferative defects S. Perez-Patrigeon1, E. Espinosa2, A. Mondragón-Eguiluz1, G. Olvera García2, U. Orbe2 1 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico 2 Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico Figure 1.- Activated pre-Th1 cells and activated pre-Th2 cells are over-represented within CD4+ TCM of HIV infected patients Figure 4.- % CD38+ pre-Th1 of CD4+ TCM cells correlated with proliferative response of CD4+ T cells to CMV Background The mechanisms linking chronic immune activation and CD4+ T cell depletion in HIV infection remain poorly understood. In chronic HIV infection, loss of remnant critical levels of effector memory CD4+ T cells has been related to a failure of central memory CD4+ T cells (TCM) to replenish this cell pool by proliferation and differentiation [1-4]. We hypothesized that TCM cells from HIV-infected patients would show an activation-driven commitment to differentiate to effector memory cells instead of proliferating upon TCR stimulation. CD38+ pre-Th1* 16.8% CD38+ pre-Th2 2.5% Pre-Th2 CD38- 6.2% Pre-Th1 CD38- 2.6% Other CD38+ 45.1% Other CD38- 17.1% 46.1% CD38+ pre-Th1 4.9% 4.6% CD38+ pre-Th2** 12.2% 8.4% 35.5% 0.5 1 1.5 2 2.5 3 3.5 Percent Ki67+ of total CD4+ T cells 5 10 15 20 25 30 35 40 HIV+ HIV- R=0.76, p=0.005 Materials and methods Using flow cytometry, CD4+ TCM were identified among PBMCs of 6 untreated HIV infected patients and 5 controls. Pre-Th1 and pre-Th2 effector-committed cells were identified as CXCR5- and either CXCR3+ or CCR4+, respectively. Activation was determined by CD38 expression. Proliferative responses to SEB and HIV and CMV peptides were determined by Ki67 induction. Groups were compared with Mann-Whitney’s U test. Variables within groups were compared using Wilcoxon’s signed rank test. Correlations between variables were determined by linear regression. Results CD4+ TCM cells from patients had higher %activated Th1-committed cells and activated Th2-committed cells than controls (p= 0.037, p=0.025 correspondingly) (Fig.1). CD4+ TCM cells with a phenotype indicating pre-Th2 differentiation commitment had a decreased polyclonal proliferative response to SEB compared with uncommitted TCM cells (p=0.043 in patients, p=0.046 in controls) (Fig.2), while pre-Th1 CD4+ TCM cells from controls proliferated less frequently than uncommitted cells in response to SEB (p=0.028) (Fig. 3). % CD38+ Pre-Th1 of TCM CD4+ Figure 5.- %CD38+ pre Th2 of TCM CD4+ cells correlated with proliferative response of CD4+ T cells to CMV Total CD4+ TCM of Healthy donors Total CD4+ TCM of HIV infected Patients .5 1 1.5 2 2.5 3 3.5 Percent Ki-67+ of total CD4+ T cells 4 5 6 7 8 9 HIV+ HIV- R=0.78, p=0.005 Pre Th1 Pre Th2 Other CD38+ Gating strategy Figure 2.- Pre-Th2 CD4+ TCM proliferated less frequently than uncommitted cells upon polyclonal stimulus PBMCs Gate: lymphocytes Gate :CD4+ T cells Gate: CD4+ T cells Gate: Tcm CD4+ Committed Gate: non-committed Gate: CXCR3+ CCR4- Gate: CXCR3- CCR4+ CD4-APC-Cy7 Ki-67-FITC Forward scatter Side scatter CCR7-PE-Cy-7 CD45RA-PE-Texas-Red CXCR5-PerCP-Cy5.5 CD38-PerCP-Cy5.5 5 10 15 20 25 30 35 40 % Ki-67+cells HIV+ HIV- *p=0.043 *p=0.046 # events # events % CD38+ pre-Th2 of TCM CD4+ Conclusions Activated central memory CD4+ T cells with a phenotype indicating commitment to differentiate to Th1 and Th2 effector memory cells are over-represented among CD4+ TCM cells from HIV+ patients. Their lower proliferative responses to TCR engagement could render CD4+ TCM less capable of regenerating the CD4+ T cell pool. The correlation between the frequency of activated and committed CD4+ TCM cells and anti-CMV response suggests that activation-associated commitment in HIV infection is partially driven by CMV infection. Pre-Th2 Uncommitted Proliferative responses of Tcm CD4+ with pre-Th2 (CXCR3- CCR4+) and uncommitted (CXCR5-) phenotype to SEB. Figure 3.- Pre-Th1 CD4+ TCM proliferated less frequently than uncommitted cells upon polyclonal stimulus only in healthy controls References 1. S. F. Sieg, C. V. Harding and M. M. Lederman, "HIV-1 infection impairs cell cycle progression of CD4(+) T cells without affecting early activation responses", Journal/J Clin Invest, vol. 108, no.5, pp. 757-764, 2001 2. M. Guadalupe, E. Reay, S. Sankaran, et al., "Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy", Journal/J Virol, vol. 77, no.21, pp. 11708-11717, 2003 3. S. Mehandru, M. A. Poles, K. Tenner-Racz, et al., "Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract", Journal/J Exp Med, vol. 200, no.6, pp. 761-770, 2004 4 . A. Okoye, M. Meier-Schellersheim, J. M. Brenchley, et al., "Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection", Journal/J Exp Med, vol. 204, no.9, pp. 2171-2185, 2007 . CXCR3-PE *p=0.028 Uncommitted Pre-Th1 5 10 15 20 25 30 35 40 % of Ki-67+cells CCR4-AF647 HIV- HIV+ Contact espinosa@iner.gob.mx, ppsyago@gmail.com Proliferative responses of TCM CD4+ with pre-Th1 (CXCR3+ CCR4-) phenotype and uncommitted (CXCR5-) phenotype to SEB.