Decreased cell-mediated immunity in patients with non-insulin-dependent diabetes mellitus.
Peripheral blood mononuclear cells from patients with non-insulin-dependent diabetes mellitus (NIDDM) show reduced proliferative response to phytohemagglutinin (PHA) and other mitogens. This study was undertaken to determine whether this reduced lymphocyte proliferation is mediated by a decreased production of cytokine or decreased expression of interleukin-2 receptor (IL-2R). Mononuclear cells from NIDDM patients (n = 34) and healthy controls (n = 22) were cultured in RPMI-1640 media containing PHA, concanavalin-A and phorbol myristate acetate. NIDDM patients showed reduced [3H]thymidine uptake (57% of controls, P < 0.01), reduced percentage of IL-2R-positive cells (61% of controls, P < 0.02) and increased level of tumor necrosis factor (TNF)-alpha (200% of controls, P < 0.05). The percentage of complement receptor (CR) 3-positive monocytes from NIDDM patients was also decreased (72% of controls, P < 0.05). However, the production of IL-1 beta, IL-2 and interferon-gamma, the percentages of pan T cells (CD3), T helper cells (CD4), T suppressor cells (CD8), the ratio of CD4/CD8 and the expression of CR1 and Fc receptors for immunoglobulin G (Fc gamma RII and Fc gamma RIII) were not significantly different between NIDDM patients and healthy subjects. Human recombinant IL-2 was unable to restore the [3H]thymidine uptake by PHA-stimulated mononuclear cells from NIDDM patients. Elevation of glucose concentration up to 27.8 mmol/l in the culture medium did not suppress the [3H]thymidine uptake and IL-2R expression by activated lymphocytes from healthy subjects. The decreased expression of IL-2R on activated lymphocytes might be responsible for the insufficient lymphocyte proliferation in NIDDM patients. These findings suggest that decreased expression of CR3 on monocytes, decreased lymphocyte proliferation and decreased IL-2R expression despite a higher production of TNF-alpha may explain the impaired cell-mediated immunity seen in NIDDM patients.
Chang
F Y
FY
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Shaio
M F
MF
D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D003208:Concanavalin A; D016207:Cytokines / Q000096:biosynthesis*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D016207:Cytokines; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine