scholarly journals IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques

Blood ◽  
2011 ◽  
Vol 118 (9) ◽  
pp. 2520-2529 ◽  
Author(s):  
Enrico Lugli ◽  
Yvonne M. Mueller ◽  
Mark G. Lewis ◽  
Francois Villinger ◽  
Peter D. Katsikis ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
Cell Loss ◽  
Treatment Interruption ◽  
Cd4 T Cell ◽  
Cell Recovery ◽  
Memory Cd8 T Cells ◽  
Highly Active

Abstract Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of memory CD4+ T cells in multiple tissues, especially at mucosal surfaces where most of these cells reside. Although antiretroviral therapy (ART) suppresses viral replication and promotes the recovery of peripheral CD4+ T cells, HIV-infected patients fail to fully reconstitute the CD4+ T-cell pool at mucosal sites. IL-15 has been shown to preferentially expand memory-phenotype T cells and promote their migration to nonlymphoid tissues. Here we examined IL-15 treatment in combination with highly active ART in chronically SIV-infected rhesus macaques and found that IL-15 delayed viral suppression and failed to enhance ART-induced total and antigen-specific CD4+ T-cell reconstitution at mucosal and lymphoid sites. IL-15 was able to induce the transient proliferation of SIV-specific, CMV-specific, and total memory CD8+ T cells, but not of SIV-specific or total CD4+ T cells. Moreover, upon treatment interruption, macaques receiving combined IL-15+ART lost CD4+ T cells faster than those receiving ART alone. These results suggest that the combination of IL-15 with highly active ART is not more efficient than ART alone in promoting CD4+ T-cell recovery in HIV-infected individuals and may accelerate CD4+ T-cell loss after treatment interruption.

scholarly journals Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract

2004 ◽  
Vol 200 (6) ◽  
pp. 761-770 ◽  
Author(s):  
Saurabh Mehandru ◽  
Michael A. Poles ◽  
Klara Tenner-Racz ◽  
Amir Horowitz ◽  
Arlene Hurley ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Cell Loss ◽  
Cd4 T Cell ◽  
Suppressive Therapy ◽  
Hiv 1 ◽  
Gi Mucosa

Given its population of CCR5-expressing, immunologically activated CD4+ T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4+ T cells would be observed in HIV-1–infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4+ T cells compared with peripheral blood CD4+ T cells is seen during primary HIV-1 infection. CD4+ T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4+ T cell population, a significantly greater CD4+ T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.

scholarly journals CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection

2021 ◽  
Author(s):  
Taylor W. Foreman ◽  
Christine E. Nelson ◽  
Keith D. Kauffman ◽  
Nickiana E. Lora ◽  
Caian L. Vinhaes ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Loss ◽  
Cd4 T Cell ◽  
Acute Hiv Infection ◽  
Macaque Model ◽  
Siv Infection ◽  
Early Effects ◽  
Pulmonary Granulomas

The HIV-mediated decline in circulating CD4 T cells correlates with increased the risk of active tuberculosis (TB). However, HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals also have an increased incidence of TB prior to loss of CD4 T cells in blood, raising the possibility that HIV co-infection leads to disruption of CD4 T cell responses at the site of lung infection before they are observed systemically. Here we used a rhesus macaque model of SIV/Mtb co-infection to study the early effects of acute SIV infection on CD4 T cells in pulmonary Mtb granulomas. Two weeks after SIV co-infection CD4 T cells were dramatically depleted from granulomas, before significant bacterial outgrowth, disease reactivation as measured by PET-CT imaging, or CD4 T cell loss in blood, airways, and lymph nodes. Mtb-specific CD4 T cells, CCR5-expressing, in granulomas were preferentially depleted by SIV infection. Moreover, CD4 T cells were preferentially depleted from the granuloma core and lymphocyte cuff relative to B cell-rich regions, and live imaging of granuloma explants showed that SIV co-infection reduced T cell motility. Thus, Mtb-specific CD4 T cells in pulmonary granulomas may be decimated before many patients even experience the first symptoms of acute HIV infection.

scholarly journals Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy

2010 ◽  
Vol 84 (18) ◽  
pp. 9010-9018 ◽  
Author(s):  
Kenneth S. Knox ◽  
Carol Vinton ◽  
Chadi A. Hage ◽  
Lisa M. Kohli ◽  
Homer L. Twigg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Bronchoalveolar Lavage ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Lavage Fluid ◽  
Cd4 T Cell ◽  
Highly Active ◽  
Before And After

ABSTRACT The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells.

scholarly journals Induction of a virus-specific effector–memory CD4+ T cell response by attenuated SIV infection

2006 ◽  
Vol 203 (12) ◽  
pp. 2661-2672 ◽  
Author(s):  
Marie-Claire Gauduin ◽  
Yi Yu ◽  
Amy Barabasz ◽  
Angela Carville ◽  
Mike Piatak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
High Frequency ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Specific Effector

We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVΔnef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4–10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5–10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVΔnef animals were predominantly CD27−CD28−CD45RAlowCCR7−CCR5−, consistent with an effector–memory subset, and included a fully differentiated CD45RA+CCR7− subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA−CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7−CD4+ subset from SIVΔnef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector–memory T cell population. The ability of SIVΔnef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.

scholarly journals Vaccination with SIVmac239Δnef activates CD4+T cells in the absence of CD4+T-cell loss

2009 ◽  
Vol 38 ◽  
pp. 8-16 ◽  
Author(s):  
R.K. Reeves ◽  
J. Gillis ◽  
F.E. Wong ◽  
R.P. Johnson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Loss ◽  
Cd4 T Cell

Raltegravir intensification shows differing effects on CD8 and CD4 T cells in HIV-infected HAART-suppressed individuals with poor CD4 T-cell recovery

AIDS ◽  
2012 ◽  
Vol 26 (18) ◽  
pp. 2285-2293 ◽  
Author(s):  
Marta Massanella ◽  
Eugènia Negredo ◽  
Jordi Puig ◽  
Maria C. Puertas ◽  
Maria J. Buzón ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Recovery

scholarly journals Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques

Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4168-4174 ◽  
Author(s):  
Xiaolei Wang ◽  
Huanbin Xu ◽  
Bapi Pahar ◽  
Xavier Alvarez ◽  
Linda C. Green ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Lymphoid Tissues ◽  
Immunodeficiency Virus

Abstract Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4+ and CD8+ T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)–infected neonates. The results demonstrate infant primates have much greater rates of CD4+ T-cell proliferation than adult macaques, and that these proliferating, recently “activated” CD4+ T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4+ T cells in acute infection. This depletion is accompanied by a marked increase in CD8+ T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4+ T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4+ T cells), which may explain the sustained “peak” viremia characteristic of pediatric HIV infection. Eventual failure of CD4+ T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.

scholarly journals The effect of tuberculosis on immune reconstitution among HIV patients on highly active antiretroviral therapy in Adigrat general hospital, eastern Tigrai, Ethiopia; 2019: a retrospective follow up study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hadush Negash ◽  
Haftom Legese ◽  
Mebrahtu Tefera ◽  
Fitsum Mardu ◽  
Kebede Tesfay ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Cd4 T Cell ◽  
Highly Active ◽  
Cell Counts

Abstract Background Ethiopia initiated antiretroviral therapy early in 2005. Managing and detecting antiretroviral treatment response is important to monitor the effectiveness of medication and possible drug switching for low immune reconstitution. There is less recovery of CD4+ T cells among human immunodeficiency virus patients infected with tuberculosis. Hence, we aimed to assess the effect of tuberculosis and other determinant factors of immunological response among human immunodeficiency virus patients on highly active antiretroviral therapy. A retrospective follow up study was conducted from October to July 2019. A total of 393 participants were enrolled. An interviewer based questionnaire was used for data collection. Patient charts were used to extract clinical data and follow up results of the CD4+ T cell. Current CD4+ T cell counts of patients were performed. STATA 13 software was used to analyze the data. A p-value ≤0.05 was considered a statistically significant association. Results The mean age of study participants was 39.2 years (SD: + 12.2 years) with 8.32 mean years of follow up. The overall prevalence of immune reconstitution failure was 24.7% (97/393). Highest failure rate occurred within the first year of follow up time, 15.7 per 100 Person-year. Failure of CD4+ T cells reconstitution was higher among tuberculosis coinfected patients (48.8%) than mono-infected patients (13.7%). Living in an urban residence, baseline CD4+ T cell count ≤250 cells/mm3, poor treatment adherence and tuberculosis infection were significantly associated with the immunological failure. Conclusions There was a high rate of CD4+ T cells reconstitution failure among our study participants. Tuberculosis infection increased the rate of failure. Factors like low CD4+ T cell baseline count, poor adherence and urban residence were associated with the immunological failure. There should be strict monitoring of CD4+ T cell counts among individuals with tuberculosis coinfection.

scholarly journals Kinetics of CD4+ T-cell recovery amongst HIV load suppressed patients on first-line antiretroviral therapy in Yaoundé, Cameroon

2021 ◽  
Vol 15 (3) ◽  
pp. 881-888
Author(s):  
Cedric Happi Mbakam ◽  
Julius Mbekem Nwobegahay ◽  
Cybelle Fodieu Mezajou ◽  
Franklin Agueguia Azebaze ◽  
Leopold Mbous Nguimbus ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Standard Form ◽  
University Teaching ◽  
Cd4 T Cell ◽  
Cell Recovery ◽  
First Line ◽  
Kinetics Of

HIV infected patients on Antiretroviral Therapy (ART) are exposed to various immunological disorders. Immune reconstitution is one of the most challenging problem linked to morbidity and mortality in HIV patients. This study aimed at evaluating the kinetics of CD4+ T-cell recovery amongst HIV load suppressed patients on first-line ART in Yaoundé, Cameroon. This was a retrospective cohort study performed at the care and treatment units of the Yaoundé University Teaching Hospital and Essos Hospital Center, with viral suppressed patients initiated on ART between March and July 2015. Data were collected using a standard form and analyzed using R.3.6.2 software. A p<0.05 was considered statistically significant for a 95%CI. Of the 499 viral suppressed participants, 32% (n=160) were male and 68% (n=339) female; 33% and 40% had severe and moderate immunodepression at baseline, respectively; 9% and 28% remain respectively on the same immunological state. CD4+ T-cell count increased by 73%, 49% and 29% for patients that started treatment, with CD4+ <150 cells/ml, 150<CD4+<350 cells/ml and 350<CD4+<500 cells/ml, respectively and 14%, 34% and 40% reached a target of 500 cells/ml or more after 4 years of treatment. Elder patients and males were likely to have CD4+ T-cells less than 350 Cells/ml. Approximately 35% of patient started treatment with CD4+ T-cells <350 Cells/ml. CD4+ T-cells increased significantly during 4 years of treatment but, just 29% in average achieved CD4+ ≥ 500 cells/ml. CD4 T-cells recovery represent and important challenge in the immunological monitoring of long-term HIV infected patients on ART.

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