Analysis of Peripheral Blood Lymphocyte Cell Surface Density of Functional and Activation Associated Markers in Young and Old Hemodialysis Patients

Abstract

Aging has been associated with specific shifts in various peripheral blood immume competent cell subsets. As part of pre-transplant immune profile evaluation possible parallel age-related changes in mean T-cell surface density of several cluster differentiation and activation linked antigens were analyzed in 150 patients with end stage renal disease on chronic hemodialysis. Patients were divided into 2 groups: group 1—114 patients 40 years old or younger and group 2—36 patients 55 years old or older. Peripheral blood CD3+, DR+, CD3+DR+, CD4+, CD4+DR+, CD8+, CD8+DR+, CD56+, CD8+CD56+, CD3+IL-2-R+ and CD3+TR+ (interleukin-2 and transferrin receptors bearing CD3+ cells respectively), all mononuclear cells expressing IL-2-R and TR, and CD4+CD45+ cell subsets were analyzed and enumerated by 2-color flow cytometry. Subset relative levels as well as absolute counts were recorded. Cell surface density computation was performed using a computerized mathematical model based on fluorescence intensity vector analysis and cell size score determination based on light scatter pattern from raw data obtained by flow cytometry studies.Younger age was significantly associated with higher absolute cell count of CD3+ (p <0.001), DR+ (p <0.05), CD4+ (p <0.01), CD8+ (p <0.005), CD3+IL-2-R+ (p <0.05), CD3+TR+ (p <0.03) and IL-2-R+ (p <0.05). Older patients had a slightly higher mean absolute count of CD4+CD45+ subset (p not significant) and significantly higher mean count for CD8+CD56+ cell subset (p <0.001). When cell subset levels were compared between the 2 groups as the relative fraction of cells expressing a given marker out of all mononuclear cells gated out by flow cytometry, younger age was significantly associated with higher levels of CD3+ (p <0.005), CD8+ (p <0.001), CD4+DR+ (p <0.004), CD3-TR+ (p <0.05) and CD8+IL-2-R+ (p <0.05). In contrast, slightly higher subset levels of CD56+ (p not significant), and significantly elevated levels of CD8+CD56+ (p <0.0019) and CD4+CD45+ (p <0.004) were observed in the older patients. Cell surface density analysis showed that younger patients had higher mean density per cell of CD3 (p <0.05), CD8 (p <0.001), IL-2-R on CD3+ cells (p <0.05) and TR on CD3+ cells (p <0.05). Mean cell surface density of CD56 on all CD56+ cells as well as on CD84-cells was higher in older individuals (p <0.001 and p <0.003, respectively). Similarly, the CD45 antigen expression on CD4+ cells was significantly increased in older patients (p <0.002).These data suggest that in parallel to specific shifts in certain cell subsets seen in elderly individuals on chronic hemodialysis, age-related changes in cell surface densities of functional cluster differentiation and activation associated markers can be detected. Such changes may reflect the decline in cell-mediated immunity in older patients on chronic hemodialysis.