scholarly journals Development of Vγ2Vδ2+T Cell Responses during Active Mycobacterial Coinfection of Simian Immunodeficiency Virus–Infected Macaques Requires Control of Viral Infection and Immune Competence of CD4+T Cells

2004 ◽  
Vol 190 (8) ◽  
pp. 1438-1447 ◽  
Author(s):  
Ling Shen ◽  
Yun Shen ◽  
Dan Huang ◽  
Liyou Qiu ◽  
Prabhat Sehgal ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Simian Immunodeficiency Virus ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Immune Competence ◽  
Cell Responses ◽  
Immunodeficiency Virus

scholarly journals Increased Loss of CCR5+ CD45RA− CD4+ T Cells in CD8+ Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys

2008 ◽  
Vol 82 (11) ◽  
pp. 5618-5630 ◽  
Author(s):  
Ronald S. Veazey ◽  
Paula M. Acierno ◽  
Kimberly J. McEvers ◽  
Susanne H. C. Baumeister ◽  
Gabriel J. Foster ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Peripheral Blood ◽  
T Cell Responses ◽  
Lymphocyte Depletion ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT Previously we have shown that CD8+ T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4+ T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8+ T-cell responses on the magnitude of the CD4+ T-cell depletion, we investigated the effect of CD8+ lymphocyte depletion during primary SIV infection on CD4+ T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8+ lymphocyte-depletion changed the dynamics of CD4+ T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4+ T cells were restored to baseline levels. These CD4+ T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8+ lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5+ CD45RA− CD4+ T cells in CD8+ lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4+ T cells were eliminated more efficiently in CD8+ lymphocyte-depleted animals. Also, CD8+ lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4+ T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8+ T-cell responses are absolutely critical to initiate at least partial control of SIV infection.

scholarly journals Reduced Protection from Simian Immunodeficiency Virus SIVmac251 Infection Afforded by Memory CD8+ T Cells Induced by Vaccination during CD4+ T-Cell Deficiency

2008 ◽  
Vol 82 (19) ◽  
pp. 9629-9638 ◽  
Author(s):  
Monica Vaccari ◽  
Joseph Mattapallil ◽  
Kaimei Song ◽  
Wen-Po Tsai ◽  
Anna Hryniewicz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Interleukin 2 ◽  
T Cell Responses ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus

ABSTRACT Adaptive CD4+ and CD8+ T-cell responses have been associated with control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication. Here, we have designed a study with Indian rhesus macaques to more directly assess the role of CD8 SIV-specific responses in control of viral replication. Macaques were immunized with a DNA prime-modified vaccinia virus Ankara (MVA)-SIV boost regimen under normal conditions or under conditions of antibody-induced CD4+ T-cell deficiency. Depletion of CD4+ cells was performed in the immunized macaques at the peak of SIV-specific CD4+ T-cell responses following the DNA prime dose. A group of naïve macaques was also treated with the anti-CD4 depleting antibody as a control, and an additional group of macaques immunized under normal conditions was depleted of CD8+ T cells prior to challenge exposure to SIVmac251. Analysis of the quality and quantity of vaccine-induced CD8+ T cells demonstrated that SIV-specific CD8+ T cells generated under conditions of CD4+ T-cell deficiency expressed low levels of Bcl-2 and interleukin-2 (IL-2), and plasma virus levels increased over time. Depletion of CD8+ T cells prior to challenge exposure abrogated vaccine-induced protection as previously shown. These data support the notion that adaptive CD4+ T cells are critical for the generation of effective CD8+ T-cell responses to SIV that, in turn, contribute to protection from AIDS. Importantly, they also suggest that long-term protection from disease will be afforded only by T-cell vaccines for HIV that provide a balanced induction of CD4+ and CD8+ T-cell responses and protect against early depletion of CD4+ T cells postinfection.

scholarly journals Inactivated Simian Immunodeficiency Virus-Pulsed Autologous Fresh Blood Cells as an Immunotherapy Strategy

2008 ◽  
Vol 83 (3) ◽  
pp. 1501-1510 ◽  
Author(s):  
Rosemarie D. Mason ◽  
Sheilajen Alcantara ◽  
Viv Peut ◽  
Liyen Loh ◽  
Jeffrey D. Lifson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
T Cell Responses ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Practical immunotherapies for human immunodeficiency virus infection are needed. We evaluated inactivated simian immunodeficiency virus (SIV) pulsed onto fresh peripheral blood mononuclear cells in 12 pigtail macaques with chronic SIVmac251 infection for T-cell immunogenicity in a randomized cross-over design study. The immunotherapy was safe and convincingly induced high levels of SIV-specific CD4+ T-cell responses (mean, 5.9% ± 1.3% of all CD4+ T cells) and to a lesser extent SIV-specific CD8+ T-cell responses (mean, 0.7% ± 0.4%). Responses were primarily directed toward Gag and less frequently toward Env but not Pol or regulatory/accessory SIV proteins. T-cell responses against Gag were generally broad and polyfunctional, with a mean of 2.7 CD4+ T-cell epitopes mapped per animal and more than half of the SIV Gag-specific CD4+ T cells expressing three or more effector molecules. The immunogenicity was comparable to that found in previous studies of peptide-pulsed blood cells. Despite the high-level immunogenicity, no reduction in viral load was observed in the chronically viremic macaques. This contrasts with our studies of immunization with peptide-pulsed blood cells during early SIV infection in macaques. Future studies of inactivated virus-pulsed blood cell immunotherapy during early infection of patients receiving antiretroviral therapy are warranted.

scholarly journals T Cell–Intrinsic CX3CR1 Marks the Most Differentiated Effector CD4+ T Cells, but Is Largely Dispensable for CD4+ T Cell Responses during Chronic Viral Infection

2020 ◽  
Vol 4 (11) ◽  
pp. 701-712
Author(s):  
Nathália V. Batista ◽  
Yu-Han Chang ◽  
Kuan-Lun Chu ◽  
Kuan Chung Wang ◽  
Mélanie Girard ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Chronic Viral Infection ◽  
Cell Responses

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 gp120 Presentation to CD4 T Cells by Antibodies Specific for the CD4 Binding Domain of gp120

2001 ◽  
Vol 75 (22) ◽  
pp. 10950-10957 ◽  
Author(s):  
Catarina E. Hioe ◽  
Michael Tuen ◽  
Peter C. Chien ◽  
Gareth Jones ◽  
Silvia Ratto-Kim ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Suppressive Effect ◽  
Binding Domain ◽  
Cell Responses ◽  
Inhibitory Mechanisms ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV)-specific CD4 T-cell responses, particularly to the envelope glycoproteins of the virus, are weak or absent in most HIV-infected patients. Although these poor responses can be attributed simply to the destruction of the specific CD4 T cells by the virus, other factors also appear to contribute to the suppression of these virus-specific responses. We previously showed that human monoclonal antibodies (MAbs) specific for the CD4 binding domain of gp120 (gp120CD4BD), when complexed with gp120, inhibited the proliferative responses of gp120-specific CD4 T-cells. MAbs to other gp120 epitopes did not exhibit this activity. The present study investigated the inhibitory mechanisms of the anti-gp120CD4BD MAbs. The anti-gp120CD4BD MAbs complexed with gp120 suppressed gamma interferon production as well as proliferation of gp120-specific CD4 T cells. Notably, the T-cell responses to gp120 were inhibited only when the MAbs were added to antigen-presenting cells (APCs) during antigen pulse; the addition of the MAbs after pulsing caused no inhibition. However, the anti-gp120CD4BD MAbs by themselves, or as MAb/gp120 complexes, did not affect the presentation of gp120-derived peptides by the APCs to T cells. These MAb/gp120 complexes also did not inhibit the ability of APCs to process and present unrelated antigens. To test whether the suppressive effect of anti-gp120CD4BDantibodies is caused by the antibodies' ability to block gp120-CD4 interaction, APCs were treated during antigen pulse with anti-CD4 MAbs. These treated APCs remained capable of presenting gp120 to the T cells. These results suggest that anti-gp120CD4BD Abs inhibit gp120 presentation by altering the uptake and/or processing of gp120 by the APCs but their inhibitory activity is not due to blocking of gp120 attachment to CD4 on the surface of APCs.

scholarly journals Gag p27-Specific B- and T-Cell Responses in Simian Immunodeficiency Virus SIVagm-Infected African Green Monkeys

2008 ◽  
Vol 83 (6) ◽  
pp. 2770-2777 ◽  
Author(s):  
José-Manuel Lozano Reina ◽  
David Favre ◽  
Zeljka Kasakow ◽  
Véronique Mayau ◽  
Marie-Thérèse Nugeyre ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Simian Immunodeficiency Virus ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Green Monkeys

ABSTRACT Nonpathogenic simian immunodeficiency virus SIVagm infection of African green monkeys (AGMs) is characterized by the absence of a robust antibody response against Gag p27. To determine if this is accompanied by a selective loss of T-cell responses to Gag p27, we studied CD4+ and CD8+ T-cell responses against Gag p27 and other SIVagm antigens in the peripheral blood and lymph nodes of acutely and chronically infected AGMs. Our data show that AGMs can mount a T-cell response against Gag p27, indicating that the absence of anti-p27 antibodies is not due to the absence of Gag p27-specific T cells.

scholarly journals Inhibition of Adaptive Vγ2Vδ2+ T-Cell Responses during Active Mycobacterial Coinfection of Simian Immunodeficiency Virus SIVmac-Infected Monkeys

2003 ◽  
Vol 77 (5) ◽  
pp. 2998-3006 ◽  
Author(s):  
Dejiang Zhou ◽  
Xiaomin Lai ◽  
Yun Shen ◽  
Prabhat Sehgal ◽  
Ling Shen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Γδ T Cells ◽  
Subsequent Development ◽  
T Cell Responses ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Adaptive immune responses of γδ T cells during active mycobacterial coinfection of human immunodeficiency virus-infected humans have not been studied. Macaques infected with the simian immunodeficiency virus (SIV) SIVmac were employed to determine the extent to which a coincident AIDS virus infection might compromise immune responses of mycobacterium-specific Vγ2Vδ2+ T cells during active mycobacterial infection. Control SIVmac-negative macaques developed primary and recall expansions of phosphoantigen-specific Vγ2Vδ2+ T cells after Mycobacterium bovis BCG infection and BCG reinfection, respectively. In contrast, SIVmac-infected macaques did not exhibit sound primary and recall expansions of Vγ2Vδ2+ T cells in the blood and pulmonary alveoli following BCG infection and reinfection. The absence of adaptive Vγ2Vδ2+ T-cell responses was associated with profound CD4+ T-cell deficiency and subsequent development of SIVmac-related tuberculosis-like disease in the coinfected monkeys. Consistently, Vγ2Vδ2+ T cells from coinfected monkeys displayed a reduced capacity to expand in vitro following stimulation with phosphoantigen. The reduced ability of Vγ2Vδ2+ peripheral blood lymphocytes (PBL) to expand could be restored to some extent by coculture of these cells with CD4+ T cells purified from PBL of SIV-negative monkeys. Furthermore, naïve monkeys inoculated simultaneously with SIVmac and BCG were unable to sustain expansion of Vγ2Vδ2+ T cells at the time that the coinfected monkeys developed lymphoid depletion and a fatal tuberculosis-like disease. Nevertheless, no deletion in Vδ2 T-cell receptor repertoire was identified in SIVmac-BCG-coinfected macaques, implicating an SIVmac-induced down-regulation rather than a clonal exhaustion of these cells. Thus, an SIVmac-induced compromise of the adaptive Vγ2Vδ2+ T-cell responses may contribute to the immunopathogenesis of the SIV-related tuberculosis-like disease in macaques.

scholarly journals Naive T cells are dispensable for memory CD4+ T cell homeostasis in progressive simian immunodeficiency virus infection

2012 ◽  
Vol 209 (4) ◽  
pp. 641-651 ◽  
Author(s):  
Afam A. Okoye ◽  
Mukta Rohankhedkar ◽  
Chike Abana ◽  
Audrie Pattenn ◽  
Matthew Reyes ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Naïve T Cells ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Siv Infection

The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4+ memory T cell (TM) homeostasis. CD4+ naive T cells (TN) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4+ TN in SIV pathogenesis using rhesus macaques (RMs) selectively and permanently depleted of CD4+ TN before SIV infection. CD4+ TN-depleted and CD4+ TN-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4+ T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4+ TM recovery, only sham-treated RMs reconstituted CD4+ TN. CD4+ TN-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4+ T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8+ T cell responses. However, CD4+ TN-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4+ TN deficiency had no significant effect on CD4+ TM homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4+ TN compartment is dispensable for CD4+ TM homeostasis in progressive SIV infection, and they confirm that CD4+ TM comprise a homeostatically independent compartment that is intrinsically capable of self-renewal.

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