Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1213-1219 ◽  
Author(s):  
Sieghart Sopper ◽  
Dagmar Nierwetberg ◽  
Astrid Halbach ◽  
Ursula Sauer ◽  
Carsten Scheller ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Cd4 T Cells ◽  
Cd4 Counts ◽  
Immunodeficiency Virus ◽  
Total Body ◽  
Spleen And Lymph Nodes ◽  
Asymptomatic Phase

HIV infection leads to reduced numbers and increased turnover of CD4+ T cells in blood. However, blood represents only 2% of the total lymphocyte pool, and information about other organs is lacking, leading to controversy about the effects of HIV infection on T-cell homeostasis. Therefore, we have determined phenotype and turnover of lymphocyte subsets in various tissues of macaques. Infection with simian immunodeficiency virus (SIV) resulted in increased proliferation rates of T cells in all organs. Despite reduced CD4 counts in blood, absolute numbers of CD4+ T cells were increased in spleen and lymph nodes and remained stable in nonlymphoid organs such as liver, lung, bone marrow, and brain during the asymptomatic phase, indicative for an altered tissue distribution. In animals killed with first signs of AIDS, total body CD4 counts and proliferation rates had returned to control levels, whereas thymocytes were almost completely absent. Our data show that a drastically increased turnover in the early stages of HIV infection, driven by a generalized immune activation rather than a homeostatic response to CD4+ T-cell destruction, is followed by exhaustion of the regenerative capacity of the immune system.

scholarly journals Relative Resistance in the Development of T Cell Anergy in CD4+T Cells from Simian Immunodeficiency Virus Disease-Resistant Sooty Mangabeys

2001 ◽  
Vol 166 (1) ◽  
pp. 506-516 ◽  
Author(s):  
Pavel Bostik ◽  
Ann E. Mayne ◽  
Francois Villinger ◽  
Kenneth P. Greenberg ◽  
Jonathan D. Powell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Cd4 T Cells ◽  
Virus Disease ◽  
Relative Resistance ◽  
T Cell Anergy ◽  
Immunodeficiency Virus ◽  
Sooty Mangabeys ◽  
Cell Anergy

scholarly journals HIV Infection Functionally Impairs Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Patrizia Amelio ◽  
Damien Portevin ◽  
Jerry Hella ◽  
Klaus Reither ◽  
Lujeko Kamwela ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Latent Tuberculosis ◽  
Cd4 T Cell ◽  
Content Type ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV) infection is the major risk factor predisposing for Mycobacterium tuberculosis progression from latent tuberculosis infection (LTBI) to tuberculosis disease (TB). Since long-term-treated aviremic HIV-infected individuals remained at higher risk of developing TB than HIV-uninfected individuals, we hypothesized that progression from LTBI to pulmonary TB (PTB) might be due not only to CD4 T-cell depletion but also to M. tuberculosis-specific CD4 T-cell functional impairment. To test this hypothesis, M. tuberculosis-specific T-cell frequencies and cytokine profiles were investigated in untreated Tanzanian individuals suffering from LTBI (n = 20) or PTB (n = 67) and compared to those of untreated M. tuberculosis/HIV-coinfected individuals suffering from LTBI (n = 15) or PTB (n = 10). We showed that HIV infection significantly reduced the proportion of Th2 (interleukin 4 [IL-4]/IL-5/IL-13) producing M. tuberculosis-specific CD4 T cells and IL-2-producing M. tuberculosis-specific CD4 and CD8 T cells in individuals with LTBI or PTB (P < 0.05). Interestingly, the loss of IL-2 production was associated with a significant increase of PD-1 expression on M. tuberculosis-specific CD4 and CD8 T cells (P < 0.05), while the loss of Th2 cytokine production was associated with a significant reduction of Gata-3 expression in memory CD4 T cells (P < 0.05). Finally, we showed that the serum levels of IL-1α, IL-6, C-reactive protein (CRP), IL-23, and IP-10 were significantly reduced in M. tuberculosis/HIV-coinfected individuals with PTB compared to those in HIV-negative individuals with PTB (P < 0.05), suggesting that HIV infection significantly suppresses M. tuberculosis-induced systemic proinflammatory cytokine responses. Taken together, this study suggests that in addition to depleting M. tuberculosis-specific CD4 T cells, HIV infection significantly impairs functionally favorable M. tuberculosis-specific CD4 T-cell responses in Tanzanian individuals with LTBI or PTB. IMPORTANCE Mycobacterium tuberculosis and human immunodeficiency virus (HIV) infections are coendemic in several regions of the world, and M. tuberculosis/HIV-coinfected individuals are more susceptible to progression to tuberculosis disease. We therefore hypothesized that HIV infection would potentially impair M. tuberculosis-specific protective immunity in individuals suffering from latent tuberculosis infection (LTBI) or active pulmonary tuberculosis (PTB). In this study, we demonstrated that M. tuberculosis/HIV-coinfected individuals have fewer circulating M. tuberculosis-specific CD4 T cells and that those that remained were functionally impaired in both LTBI and PTB settings. In addition, we showed that HIV infection significantly interferes with M. tuberculosis-induced systemic proinflammatory cytokine/chemokine responses. Taken together, these data suggest that HIV infection impairs functionally favorable M. tuberculosis-specific immunity.

scholarly journals Gut Mucosal FOXP3+ Regulatory CD4+ T Cells and Nonregulatory CD4+ T Cells Are Differentially Affected by Simian Immunodeficiency Virus Infection in Rhesus Macaques

2010 ◽  
Vol 84 (7) ◽  
pp. 3259-3269 ◽  
Author(s):  
Kristina Allers ◽  
Christoph Loddenkemper ◽  
Jörg Hofmann ◽  
Anett Unbehaun ◽  
Désirée Kunkel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
Virus Production ◽  
Cell Pool ◽  
Immunodeficiency Virus ◽  
Gut Mucosa ◽  
Siv Infection

ABSTRACT The gastrointestinal tract represents a major site for human and simian immunodeficiency virus (HIV and SIV) replication and CD4+ T-cell depletion. Despite severe depletion of mucosal CD4+ T cells, FOXP3+ regulatory CD4+ T cells (Treg) are highly increased in the gut mucosa of chronically HIV-infected individuals and may contribute to HIV pathogenesis, either by their immunosuppressive function or as a significant target cell population for virus production. Little is known about the susceptibility of mucosal Treg to viral infection and the longitudinal effect of HIV/SIV infection on Treg dynamics. In this study, we determined the level of SIV infection in Treg and nonregulatory CD4+ T cells (non-Treg) isolated from the colon of SIV-infected rhesus macaques. The dynamics of mucosal Treg and alterations in the mucosal CD4+ T-cell pool were examined longitudinally. Our findings indicate that mucosal Treg were less susceptible to productive SIV infection than non-Treg and thus were selectively spared from SIV-mediated cell death. In addition to improved survival, local expansion of Treg by SIV-induced proliferation of the mucosal CD4+ T-cell pool facilitated the accumulation of mucosal Treg during the course of infection. High frequency of mucosal Treg in chronic SIV infection was strongly related to a reduction of perforin-expressing cells. In conclusion, this study suggests that mucosal Treg are less affected by productive SIV infection than non-Treg and therefore spared from depletion. Although SIV production is limited in mucosal Treg, Treg accumulation may indirectly contribute to viral persistence by suppressing antiviral immune responses.

scholarly journals Enhanced Human Immunodeficiency Virus-1 Replication in CD4+ T Cells Derived From Individuals With Latent Mycobacterium tuberculosis Infection

2020 ◽  
Vol 222 (9) ◽  
pp. 1550-1560 ◽  
Author(s):  
Xianbao He ◽  
Jared J Eddy ◽  
Karen R Jacobson ◽  
Andrew J Henderson ◽  
Luis M Agosto
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Infection Status ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Background Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection. Methods Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication. Results We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells. Conclusions Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.

scholarly journals Changes in cytokine secretion patterns of CD4+ T-cell clones in human immunodeficiency virus infection

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4262-4268 ◽  
Author(s):  
L Meyaard ◽  
SA Otto ◽  
IP Keet ◽  
RA van Lier ◽  
F Miedema
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Cytokine Secretion ◽  
Ifn Gamma ◽  
T Cell Clones ◽  
Cell Clones ◽  
Immunodeficiency Virus

In addition to the loss of CD4+ T cells in later stages of human immunodeficiency virus (HIV) infection, functional defects of Th cells can already be observed in early infection. Decreased interleukin (IL)- 2 and interferon (IFN)-gamma production by CD4+ T cells and diminished delayed type hypersensitivity reactions are indicative for impaired Th1 responses. We studied the cytokine secretion patterns of T-cell clones (TCC) generated by mitogenic stimulation of CD4+ memory T cells. Compared with TCC from HIV-negative controls, TCC isolated from HIV- infected individuals consistently showed increased IL-4 production, often paralleled by increased IL-5 and decreased IFN-gamma production. This resulted in a decreased percentage of Th1 clones with an increase in Th0 clones. To rule out the influence of interindividual differences, we studied two individuals from whom cells were available before and after infection with HIV. Indeed, an increase in Th2 cytokine secretion was observed after HIV-infection. Loss of Th1 and enhanced Th2 responses might further curtail cellular responses resulting in deficiency of cellular immunity in HIV infection.

Human Immunodeficiency Virus Type 1 Protease Inhibitor Modulates Activation of Peripheral Blood CD4+ T Cells and Decreases Their Susceptibility to Apoptosis In Vitro and In Vivo

Blood ◽  
1999 ◽  
Vol 94 (3) ◽  
pp. 1021-1027 ◽  
Author(s):  
Elaine M. Sloand ◽  
Princy N. Kumar ◽  
Sonnie Kim ◽  
Aniruddho Chaudhuri ◽  
Frank F. Weichold ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cd4 Cells ◽  
Immunodeficiency Virus

CD4+ T cells from patients with human immunodeficiency virus (HIV) infection undergo apoptosis at an increased rate, which leads to their depletion during disease progression. Both the Fas-Receptor (Fas-R) and interleukin-1β (IL-1β)–converting enzyme (ICE; caspase 1) appear to play a role in the mechanism of apoptosis of CD4+ lymphocytes. Although Fas-R is upregulated on both CD4+ and CD8+ cells in HIV-infected patients, results from our laboratory and others indicate that, in patients with advanced disease, CD4+ cells preferentially express ICE. Protease inhibitors have successfully halted the progression of HIV disease and increased CD4+ T counts. In this study, we examined the effect of protease inhibitors on Fas-R (CD95), ICE (caspase 1) expression, apoptosis, and cell death in CD4+ T cells of (1) HIV-infected patients who were receiving protease inhibitors, and (2) normal and patient CD4+ T cells cultured with a protease inhibitor in vitro. Fifteen patients with advanced HIV disease on treatment showed dramatically decreased CD4+ T-cell ICE expression, diminished apoptosis, and increased numbers of CD4+ cells within 6 weeks of institution of protease inhibitor therapy, and before down-modulation of Fas-R (CD95) expression was evident. To determine the role of HIV infection, we studied the effect of ritonavir, a protease inhibitor, on normal and patient cells in vitro. Stimulated and unstimulated normal CD4+ T cells, cultured with protease inhibitor, demonstrated markedly decreased apoptosis and ICE expression (P = .01). While Fas-R expression was not significantly altered during short-term culture by such treatment, Fas-Ligand (Fas-L) membrane expression of phytohemagglutinin (PHA)-stimulated blood lymphocytes was decreased by protease inhibitor. In the presence of ritonavir, CD4+ T cells from HIV-infected patients showed similar changes in ICE intracellular levels without alteration of Fas expression. In conclusion, protease inhibitors appear to decrease CD4+ T-cell ICE expression and apoptosis before they affect Fas-R expression in HIV-infected patients. This action was independent of HIV infection, as similar effects were seen in CD4+ T cells from normal controls. Some of the benefit of protease inhibitors may be related to modification of programmed cell death, which increases CD4+ T-cell number. Whether this is due to directly to the changes effected in the caspase system remains to be determined.

scholarly journals Distinct Cycling CD4+- and CD8+-T-Cell Profiles during the Asymptomatic Phase of Simian Immunodeficiency Virus SIVmac251 Infection in Rhesus Macaques

2003 ◽  
Vol 77 (18) ◽  
pp. 10047-10059 ◽  
Author(s):  
V. Monceaux ◽  
R. Ho Tsong Fang ◽  
M. C. Cumont ◽  
B. Hurtrel ◽  
J. Estaquier
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Chronic Phase ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Asymptomatic Phase

ABSTRACT Elevated CD4 T-cell turnover may lead to the exhaustion of the immune system during human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) infections. However, this hypothesis remains controversial. Most studies of this subject have concerned the blood, and information about the lymph nodes is rare and controversial. We used Ki67 expression to measure cycling T cells in the blood and lymph nodes of uninfected macaques and of macaques infected with a pathogenic SIVmac251 strain or with a nonpathogenic SIVmac251Δnef clone. During the asymptomatic phase of infection, the number of cycling CD8+ T cells progressively increased (two- to eightfold) both in the blood and in the lymph nodes of macaques infected with SIVmac251. This increase was correlated with viral replication and the progression to AIDS. In contrast, no increases in the numbers of cycling CD4+ T cells were found in the blood or lymph nodes of macaques infected with the pathogenic SIVmac251 strain in comparison with SIVmac251Δnef-infected or healthy macaques during this chronic phase. However, the lymph nodes of pre-AIDS stage SIVmac251-infected macaques contained more cycling CD4+ T cells (low baseline CD4+-T-cell counts in the blood). Taken together, these results show that the profiles of CD4+- and CD8+-T-cell dynamics are distinct both in the lymph nodes and blood and suggest that higher CD4+-T-cell proliferation at the onset of AIDS may lead to the exhaustion of the immune system.

scholarly journals Dynamics of CCR5 Expression by CD4+ T Cells in Lymphoid Tissues during Simian Immunodeficiency Virus Infection

2000 ◽  
Vol 74 (23) ◽  
pp. 11001-11007 ◽  
Author(s):  
Ronald S. Veazey ◽  
Keith G. Mansfield ◽  
Irene C. Tham ◽  
Angela C. Carville ◽  
Daniel E. Shvetz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Cell Loss ◽  
Lymphoid Tissues ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Spleen And Lymph Nodes

ABSTRACT Early viral replication and profound CD4+ T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). Here we show that a much higher percentage of CD4+ T cells in the intestine express CCR5 compared with those found in the peripheral blood, spleen, or lymph nodes. In addition, the selectivity and extent of the CD4+ T-cell loss in SIV infection may depend upon these cells coexpressing CCR5 and having a “memory” phenotype (CD45RA−). Following intravenous infection with SIVmac251, memory CD4+ CCR5+ T cells were selectively eliminated within 14 days in all major lymphoid tissues (intestine, spleen, and lymph nodes). However, the effect on CD4+T-cell numbers was most profound in the intestine, where cells of this phenotype predominate. The CD4+ T cells that remain after 14 days of infection lacked CCR5 and/or were naive (CD45RA+). Furthermore, when animals in the terminal stages of SIV infection (with AIDS) were examined, virtually no CCR5-expressing CD4+ T cells were found in lymphoid tissues, and all of the remaining CD4+ T cells were naive and coexpressed CXCR4. These findings suggest that chemokine receptor usage determines which cells are targeted for SIV infection and elimination in vivo.

Sign in / Sign up

Export Citation Format

Share Document