Lymphopenia in dialysis patients: a preliminary study indicating a possible role of apoptosis.
Lymphopenia is a common finding in dialysis patients. Since infection rate and mortality associated with infection are high in dialysis patients, lymphopenia may be one of the contributing factors. In the present study, we evaluated the mechanism responsible for lymphopenia in these patients. Lymphocytes isolated from dialysis patients showed increased apoptosis (p < 0.001) when compared to lymphocytes isolated from healthy subjects (healthy subjects, 0.5 +/- 0.2% vs. dialysis patients, 8.8 +/- 0.7% apoptotic cells/field). Sera from dialysis patients promoted lymphocyte apoptosis in a time- and dose-dependent manner. These sera also enhanced lymphocyte DNA fragmentation into multiple integers of 180 base pairs in the form of a ladder pattern. Cellulose acetate membranes promoted T cell apoptosis when compared to polysulfone membranes and to control. Cellulose acetate dialysis membranes also appear to promote lymphocyte FasL expression. Similarly, dialysis sera enhanced T cell Fas as well as FasL expression. Neither the cellulose acetate nor polysulfone membranes could induce FasL expression on B cells. Similarly, dialysis sera failed to induce FasL expression on B cells. On the other hand, anti-FasL antibodies attenuated dialysis sera-induced apoptosis in T as well as B cells. Interestingly, dialysis serum showed a 5-fold increase in FasL content when compared with control serum. These results suggest that dialysis-associated factors can induce autocrine death in T cells but the help of activated T cells is required to induce death in B cells.
Bhaskaran
M
M
Division of Kidney Diseases and Hypertension, Long Island Jewish Medical Center and North Shore University Hospital, New York, NY 11040, USA.
Ranjan
R
R
Shah
H
H
Siu
J
J
Colvin
R
R
Radhakrishnan
N
N
Reddy
K
K
Franki
N
N
Wagner
J D
JD
Singhal
P C
PC
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D001769:Blood; D002460:Cell Line; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D008231:Lymphopenia / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor