Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage HIV-1 disease

Mezzaroma, Ivano; Carlesimo, M; Pinter, Elena; Alario, C; Sacco, Giovanna; Muratori, Donatella Santini; Bernardi, Maria Livia; Paganelli, Roberto; Aiuti, F

doi:10.1097/00002030-199907090-00006

Cited by 109 publications

(71 citation statements)

References 22 publications

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“…Under HAART, a significant increase in the lymphocyte proliferative responses to anti-CD3 and PHA, despite persisting high viral load, have been reported [37]. In our study, the recovery of the in vitro T-lymphocyte response was earlier and sustained over time for those mitogens which explore exclusively T-lymphocyte reactivity (PHA) compared with those that induce both B and T-lymphocyte responses (PWM).…”

Section: Discussionsupporting

confidence: 47%

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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Section: Discussionsupporting

confidence: 47%

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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“…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: 55%

“…The pelleted RNA was resuspended in diethyl-pyrocarbonate-treated water and the poly (A) 1 portion of total RNA, was converted into cDNA using 2´5 mm oligo(dT) (Perkin Elmer, Norwalk, CT, USA) and 2´5 units MULV reverse transcriptase (Perkin Elmer). The sequences of 24 TCRBV subfamilies specific primers (BV 1, 2, 3, 4, 5´1, 5´3, 6´1, 6´2, 7,8,9,11,12,13,14,15,16,17,18,20,21,22,23,24) and of a TCR constant b-chain (BC) primer used in this study were previously described by Maslanka et al [20]. Amplications of target cDNA were performed as reported by Gorochov et al [5].…”

Section: Study Populationmentioning

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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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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“…While repopulation by naïve CD4 ϩ T lymphocytes from the thymus can demonstrably lead to immunoreconstitution (10,19), generation of memory and effector Th cells, which are essential in providing help to B cells and cytotoxic T lymphocytes, will not occur unless there is sufficient antigenic exposure (27). This was demonstrated in studies of the in vitro T-cell proliferative responses of HAART-treated adults, in whom the responses to antigens to which the immune system was constantly exposed were restored more frequently (C. albicans) than the responses to an antigen to which the level of exposure was low (tetanus toxoid) ( 22,27,33). Thus, HIV-1-specific Th cells and cytotoxic T lymphocytes are poorly stimulated when the viral load is effectively suppressed by HAART (11,16,18,27,28).…”

Section: Discussionmentioning

confidence: 99%

Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Children: Analysis of Cellular Immune Responses

Blazevic¹,

Jankelevich

Steinberg

et al. 2001

Clin Diagn Lab Immunol

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The present study analyzes the effect of highly active antiretroviral therapy (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)-infected children over a 24-week period following initiation of HAART with ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included cytokine production by monocytes as well as T-cell proliferation in response to mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides. Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4 ؉ T-cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH) response. At enrollment the children exhibited defects in several immune parameters measured. Therapy increased CD4؉ T-cell counts and decreased viral loads significantly. By contrast, the only immunological parameter that was significantly increased was IL-12 p70 production by monocytes; the DTH response to Candida albicans also showed a strong increase in patients becoming positive. In conclusion, these results demonstrate that HAART in HIV-infected children affects the dynamics of HIV replication and the CD4 ؉ T-cell count over 24 weeks, similar to the pattern seen in HIV-infected adults. Furthermore, these data indicate improvement in antigen-presenting cell immunological function in HIV-infected children induced by HAART.

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Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage HIV-1 disease

Abstract: The immune recovery observed is slower and not complete in severely immunocompromised patients. Our data suggest that HAART may be continued also in the absence of a significant HIV RNA decrease if alternative drugs are not available.

Cited by 109 publications

References 22 publications

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

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

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 in Human Immunodeficiency Virus Type 1-Infected Children: Analysis of Cellular Immune Responses

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