Changes In T-cell Populations Research Articles

Quantitative Changes In T-Cell Populations After Left Ventricular Assist Device Implantation

Background—Left ventricular assist devices (LVADs) are currently being evaluated as permanent therapy for end-stage heart failure. Because life-threatening infections limit successful long-term device implantation, we investigated the relationship between quantitative T-cell defects in LVAD recipients and CD95-mediated T-cell apoptosis.Methods and Results—Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management. Fluorochrome-labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recipients had a relative lymphopenia and reduction in CD4 T-cell levels compared with NYHA class IV heart failure controls. These observations were confirmed in a longitudinal study in LVAD recipients, which showed that device implantation was accompanied by progressive and sustained reductions in circulating CD4 T-cell levels. These abnormalities in LVAD recipients were accompanied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2-fold greater for CD4 T cells than for CD8 T cells.Conclusions—These results suggest that the reduction in CD4 T-cell levels accompanying LVAD implantation is a consequence of an augmented pathway of CD95-mediated apoptosis. The clinical consequences of these abnormalities may include increased prevalence of systemic infections.

Quantitative changes in T-cell populations after left ventricular assist device implantation: relationship to T-cell apoptosis and soluble CD95.

Left ventricular assist devices (LVADs) are currently being evaluated as permanent therapy for end-stage heart failure. Because life-threatening infections limit successful long-term device implantation, we investigated the relationship between quantitative T-cell defects in LVAD recipients and CD95-mediated T-cell apoptosis. Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management. Fluorochrome-labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recipients had a relative lymphopenia and reduction in CD4 T-cell levels compared with NYHA class IV heart failure controls. These observations were confirmed in a longitudinal study in LVAD recipients, which showed that device implantation was accompanied by progressive and sustained reductions in circulating CD4 T-cell levels. These abnormalities in LVAD recipients were accompanied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2-fold greater for CD4 T cells than for CD8 T cells. These results suggest that the reduction in CD4 T-cell levels accompanying LVAD implantation is a consequence of an augmented pathway of CD95-mediated apoptosis. The clinical consequences of these abnormalities may include increased prevalence of systemic infections.

Chronic Marginal Vitamin A Status Affects the Distribution and Function of T Cells and Natural T Cells in Aging Lewis Rats

Although both vitamin A (VA) deficiency and aging are independently associated with alterations in immune function, the effects of marginal VA status or VA supplementation on the immune system during aging were not studied. A long-term dietary study was conducted in a rat model of aging to quantify changes in T-cell populations in blood and spleen, including T-cells bearing a marker of natural killer (NKT) cells. The study included nine treatment groups [three levels of dietary VA: marginal (0.35 RE/kg diet), control (4.0 RE/kg diet), and supplemented (50 RE/kg diet); and three age groups: young (2–3 mo), middle-aged (8–10 mo), and old 20–22 mo); diets were fed continuously from weaning to the end of the study period. CD3+/CD4+ T-cells decreased in percentage and number in blood with age, CD8+ cells increased (%), and the CD4/CD8 ratio decreased. Conversely, aging was associated with increased NKT cells (phenotype CD3intermediate/NKR-P1+). Based on regression analysis of flow cytometry data, the phenotype of most NKT cells was CD3intermediate/NKR-P1+/CD28−. NKT cells, which are most likely of extrathymic origin, accounted for most of the decrease in the CD4/CD8 ratio. Marginal VA status, particularly in older rats, was associated with increases in the percentage of CD8+ T cells, percentage and number of NKT cells, and peripheral blood cell anti-CD3ε-stimulated proliferative response, and decreases in the CD4/CD8 T-cell ratio and splenic cell interleukin-2 production. These differences and the reciprocal changes observed for NKT cells vs. T- and classical NK cells in aging VA-marginal rats suggest that low VA status during aging may increase the risk of infectious or neoplastic diseases that require a normal balance of T-cell or NK-cell responses.