Increased Expression of Activation Markers on CD8 Lymphocytes in Children with Human Immunodeficiency Virus-1 Infection

Schlesinger, Michael; Peters, Vicki B.; Jiang, Jian Dond; Roboz, Julia P.; Bekesi, J. George

doi:10.1203/00006450-199509000-00020

Cited by 39 publications

(18 citation statements)

References 20 publications

(33 reference statements)

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“…These data suggest that in children, activated T cells (CD4 + CD38 + HLA-DR + and CD4 + HLA-DR + ) are associated directly with VL [19]. The relationship between CD38 expression in CD4 + T cells and VL showed a different pattern compared with that between HLA-DR and VL, due probably to the influence of age and cell type on the expression of CD38 [8,[36][37][38][39]. Contrary to adults, CD4 + CD38 + is not a good disease progression marker in HIV-infected children [11,[40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Stimulated proliferative responses in vertically HIV-infected children on HAART correlate with clinical and immunological markers

Resino

Abad

Navarro

et al. 2003

Clinical and Experimental Immunology

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SUMMARYThe objective of the study was to investigate the relationship between various CD4 + T cell subsets and the ability of peripheral blood mononuclear cells (PBMC) to proliferate to several stimuli in vertically human immunodeficiency virus type 1 (HIV-1)-infected children. We studied 29 HIV-1-infected children on highly active antiretroviral therapy (HAART) (median duration: 12·3 months). T cell subsets were determined by flow cytometry. Plasma viral load (VL) was quantified using a standardized molecular method. Proliferative responses were evaluated by [ 3 H]-thymidine incorporation. Decreased proliferative responses of PBMC to pokeweed mitogen (PWM) were found for HIV-1-infected children in Centers for Disease Control (CDC) clinical categories B and C when compared to the control group ( P < 0·05). Similarly, children with £ 15% CD4 + T cells showed a decrease in proliferative responses to PWM ( P < 0·01), anti-CD3 + anti-CD28 ( P < 0·01) and phytohaemagglutinin (PHA) ( P < 0·05) with respect to the control group and to children with CD4 + T cells ≥ 25%. Proliferative responses to PWM, anti-CD3 + , anti-CD28 and PHA had a statistically significant positive correlation with CD3 + /mm 3 , CD4 + /mm 3 , % CD4 T cells, CD4/CD8 ratio and the percentage of naive T cell subsets (CD4 + CD45RO -HLA-DR -, CD4 + CD45RA + CD62L + , CD4 + CD45RA + ), CD4 + CD62L + and CD4 + T cells co-expressing CD38 + (CD4 + HLA-DR -CD38 + , CD4 + CD38 + ). Moreover, we found a negative correlation between PBMC proliferative responses and % CD8 T cells, memory, memory-activated and activated CD4 + T cell subsets. Lower proliferative responses to PWM ( P < 0·01) and PHA ( P < 0·01) were associated with higher VL. Our data show that higher proliferative responses to PWM, anti-CD3 + anti-CD28 and PHA are associated with both non-activated and naive CD4 + T cell subsets in HIV-1-infected children on HAART.

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Section: Discussionmentioning

confidence: 99%

Stimulated proliferative responses in vertically HIV-infected children on HAART correlate with clinical and immunological markers

Resino

Abad

Navarro

et al. 2003

Clinical and Experimental Immunology

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“…In adult patients infected with the human immunodeficiency virus (HIV), an increase in the percentage of CD8ϩCD38ϩ T cells and/or an increase in level of expression of CD38 on CD8ϩ T cells are indicators of a poor prognosis (7,12,13). In comparing HIV-infected versus noninfected children, results are variable (18,19,21,25). The only data that include newborn children must be interpreted with caution because the results were obtained from unspecified mixtures of cord blood and peripheral venous blood specimens (21).…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte subpopulations in healthy 1-3-day-old infants

et al. 1998

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The primary objective of this study was to establish reference ranges for the major (B, T, and natural killer; NK) and clinically relevant minor lymphocyte subsets in the peripheral blood of healthy 1–3‐day‐old infants and then to compare the results with those obtained in a group of healthy adults analyzed simultaneously. Forty‐three infants aged 1–3 days and 38 healthy adults were recruited to the study to establish the median, 10th, and 90th percentiles of the proportions and absolute numbers of relevant lymphocyte subsets. The samples obtained from the healthy adults served as a flow cytometry process control in addition to providing a group comparator. The peripheral blood of the newborns (vs. adults) contained elevated proportions of total T cells (83% vs. 77%) and T helper cells (63% vs. 46%), with decreased proportions of T suppressor/cytotoxic cells (23% vs. 28%) and NK cells (4% vs. 10.5%). The newborns had a higher proportion (P < 0.0001) of immature B lymphocytes compared with those of adults (CD10+CD19+, 1.5% vs. 0% and CD20+CD5+, 13% vs. 6%), and the proportion of activated T cells was significantly lower (P < 0.0001; CD3+CD25+, 7.0% vs. 15%;CD3+HLA‐DR+, 2.0% vs. 6% and CD8 and CD57, 0.0% vs. 8.0%). In contrast, the proportions of neonatal CD8 cells expressing CD28 (90.2% vs. 67.7%) and CD38 (96.6% vs. 70.9%) were significantly higher (P < 0.0001). The reference ranges for 1–3‐day‐old healthy newborns generated in this study provides a valuable tool for the assessment of immune abnormalities in very young infants. Cytometry (Comm. Clin. Cytometry) 34:235–241, 1998. © 1998 Wiley‐Liss, Inc.

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“…We hypothesize that CD127 expression on CD8+ T-cells may help to guide clinical management, particularly when CD4+ T-cell count and viral load findings are discrepant. The promise of CD127 expression on CD8+ T cells as an immunological correlate was shown when we compared expression of this marker with that of CD38 on CD8+ T cells, a more established marker [24], [27], [28]–CD127 expression was invariably correlated better with HIV viral load and CD4+ T cell counts.…”

Section: Discussionmentioning

confidence: 99%

CD8+ T-Cell Interleukin-7 Receptor Alpha Expression as a Potential Indicator of Disease Status in HIV-Infected Children

et al. 2008

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BackgroundInitiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease.MethodsIn a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status.Results51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers.ConclusionsCD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression.

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Increased Expression of Activation Markers on CD8 Lymphocytes in Children with Human Immunodeficiency Virus-1 Infection

Cited by 39 publications

References 20 publications

Stimulated proliferative responses in vertically HIV-infected children on HAART correlate with clinical and immunological markers

Stimulated proliferative responses in vertically HIV-infected children on HAART correlate with clinical and immunological markers

Lymphocyte subpopulations in healthy 1-3-day-old infants

CD8+ T-Cell Interleukin-7 Receptor Alpha Expression as a Potential Indicator of Disease Status in HIV-Infected Children

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