Positive Effects of Combined Antiretroviral Therapy on CD4
            <sup>+</sup>
            T Cell Homeostasis and Function in Advanced HIV Disease

Autran, Brigitte; Carcelain, Guislaine; Li, T. S.; Blanc, Catherine; Mathez, Dominique; Tubiana, Roland; Katlama, Christine; Debré, Patrice; Leibowitch, Jacques

doi:10.1126/science.277.5322.112

Cited by 1,700 publications

(1,037 citation statements)

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“…The T cell response was characterized by an early rise of naive and memory cells both in CD4 1 and CD8 1 T cells. In previuos studies designed to characterize the HAART-induced T cell repopulation in patients with advanced HIV disease, an increase of CD4 1 naive T cells was observed beginning from 6 to 12 months of therapy [2,3,23]. The faster increase in CD4 1 naive cells observed herein could be explained by a lesser HIV-induced blockade of T cell renewal occurring in patients with moderate immunodeficiency as well as to a more preserved thymic tissue [24].…”

Section: Discussionmentioning

confidence: 54%

“…However, in spite of intense investigation, the mechanisms underlying HAART-induced immune reconstitution remain to be fully characterized. Initial studies performed on HIV-1 infected patients with advanced disease suggested that HAART-induced T cell repopulation was mainly due to an early recirculation of memory cells from lymphoid tissues to blood, accompanied by a slow production of newly generated naive T cells [2,3]. More recently, a correlation between the size of thymic tissue and the magnitude of naive T cell recovery after HAART has been demonstrated, suggesting a critical role for the thymus in lymphocyte restoration [4].…”

Section: Introductionmentioning

confidence: 99%

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T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

Giovannetti

Pierdominici

Mazzetta

et al. 2001

Clinical and Experimental Immunology

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SUMMARYThe immunological correlates of highly active antiretroviral therapy (HAART)-induced suppression of human immunodeficiency virus type 1 (HIV-1) replication have been investigated. 20 HIV-1-infected patients with mean CD4 1 T cell count of 298/m l, plasma viral load of 4´7 log 10 copies/ml and naive for protease inhibitors (PI) were studied during12 months of HAART. An increased number of both CD4 1 and CD8 1 naive T cells and a normalization of the frequency of CCR5-and CXCR4-expressing CD4 1 T cells were readily observed after starting therapy. Single cell analysis of cytokine production after 12 months of HAART showed an increased number of interleukin (IL)-2-, but not IL-4-and (IFN)-g-, producing T cells and a decreased percentage of CD8 1 IFN-g 1 cells. A correlation between the frequency of IFN-g-producing T cells and that of memory, CCR5 1 and CD95 1 T cells was demonstrated in both CD4 1 and CD8 1 subsets. The diversity of T cell receptor (TCR) variable beta (BV) chain repertoire significantly increased after 12 months of HAART within the CD4 1 but not the CD8 1 T cell subset. However, the level of perturbation of the third complementaritydetermining region (CDR3), was not significantly modified by effective therapy. The number of anti-HIV Gag and Pol cytotoxic T lymphocytes precursors (CTLp) decreased during HAART and highly correlated with the CD8 IFN-g response. Ameliorated clinical conditions were observed in all patients in absence of any opportunistic infections during all the study period. These observations indicate that a better restoration of immunity may be obtained in patients starting HAART at less advanced stages of the disease.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

Giovannetti

Pierdominici

Mazzetta

et al. 2001

Clinical and Experimental Immunology

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“…It has been reported that HAART induces an improvement in CD4 + T-lymphocyte reactivity for clinically relevant pathogens [3,4,17]. However, the restoration of antigen-specific T-lymphocyte responses was closely related with an increase in CD4 + T-lymphocyte numbers [17] and was associated (in the majority of cases) with a suppression of viral load.…”

Section: Discussionmentioning

confidence: 98%

“…This decrease is associated with a progressive impairment of immune function. Highly active antiretroviral therapy (HAART, including at least 1 protease inhibitor [PI]), allows for a significant decrease in plasma and tissue HIV-1 RNA load, as well as a quantitative recovery of peripheral CD4 + T-lymphocytes in the majority of adults with HIV-1 infection [2][3][4][5] resulting in a significant reduction in morbidity and mortality [6]. However, the mechanisms governing immune improvement under HAART are still controversial.…”

Section: Introductionmentioning

confidence: 99%

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Peruzzi

Azzari

Galli

et al. 2002

Clinical and Experimental Immunology

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SUMMARY To analyse the effect of highly active antiretroviral therapy (HAART) on T-lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART. Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+, CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen) and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children were studied as controls. A gain in body weight, no worsening of the disease and no recurrence of opportunistic infections were observed. At baseline, the majority of the children had low responses to mitogens, and all of them had a defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations below the mean result for controls). During HAART, a significant increase in the response to mitogens and antigens was observed in all the patients. The T-lymphocyte response was restored more consistently against antigens to which the immune system is constantly exposed (Candida albicans, baseline versus 12 months: P < 0·001) compared with a low-exposure antigen (tetanus toxoid, baseline versus 12 months: P < 0·01). HAART restores in vitro T-lymphocyte responses even in the absence of a significant viral load decrease and despite any significant increase in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved in the overall immune recovery under HAART.

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“…Thus, it remains an open question concerning whether MG is an autoimmune disease that occurs in the thymus owing to a thymic autoantigen or is a systemic autoimmune disease with peripheral immune cell trafficking to the thymus. to rises in CD4 +, CD45RA § (putative naive) T cells (53)(54)(55). However, antiretroviral therapyinduced CD4+ T cell rises do not usually reach normal pre-HIV-1 infection levels.…”

Section: And 7)mentioning

confidence: 99%

The human thymus

Haynes

Hale

1998

Immunol Res

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The human thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T cell repertoire. Although the thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human postnatal thymus decreases over time. With the advent of intensive chemotherapy regimens for a variety of cancer syndromes, and the discovery that infection with the Human Immunodeficiency Virus (HIV) leads to severe loss of CD4 + T cells, has come the need to understand the role of the human thymus in reconstitution of the immune system in adults. During a recent study of the thymus in HIV infection, we observed many CD8 + T cells in AIDS thymuses that had markers consistent with those of mature effector cytotoxic T cells usually found in peripheral immune tissues, and noted these CD8 + effector T cells were predominately located in a thymic zone termed the thymic perivascular space. This article reviews our own work on the thymus in HIV-1 infection, and discusses the work of others that, taken together, suggest that the thymus contains peripheral immune cell components not only in the setting of HIV infection, but also in myasthenia gravis, as well as throughout normal life during the process of thymus involution. Thus, the human thymus can be thought of as a chimeric organ comprised of both central and peripheral lymphoid tissues. These observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-I infection, and thymic involution may in part derive from cytokines or other factors produced by peripheral immune cells within the thymic perivascular space.

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Positive Effects of Combined Antiretroviral Therapy on CD4 ⁺ T Cell Homeostasis and Function in Advanced HIV Disease

Cited by 1,700 publications

References 30 publications

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

The human thymus

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Positive Effects of Combined Antiretroviral Therapy on CD4 + T Cell Homeostasis and Function in Advanced HIV Disease

Cited by 1,700 publications

References 30 publications

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

T cell responses to highly active antiretroviral therapy defined by chemokine receptors expression, cytokine production, T cell receptor repertoire and anti-HIV T-lymphocyte activity

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

The human thymus

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Product

Resources

About

Positive Effects of Combined Antiretroviral Therapy on CD4 ⁺ T Cell Homeostasis and Function in Advanced HIV Disease