T lymphocytes from autoimmune thrombocytopenic purpura show a defective activation and proliferation after cytoplasmic membrane and intracytoplasmic mitogenic signals.
T lymphocyte activation and proliferation are complex cellular processes involving membrane and cytoplasmatic molecules as well as the secretion and response to cytokines, mainly interleukin 2. There is increasing evidence that autoimmune thrombocytopenic purpura (ATP) is associated with an alteration of the regulation of the immune system. The blastogenic response of purified T lymphocytes to mitogens that interact with membrane molecules (phytohemaglutinin, anti-CD3 monoclonal antibody) and with intracytoplasmic protein kinase C (phorbol myristate acetate) has been investigated in 22 ATP patients and 18 healthy controls. After the signal given by the three different mitogens [3H]-thymidine uptake in T lymphocytes from ATP patients was found to be significantly decreased with respect to that found in healthy controls under similar experimental conditions (P < 0.05). Analysis of the cell cycle progression in these T lymphocytes from ATP patients, showed a significantly diminished percentage of cells in S-phase after PHA stimulation (P < 0.05). The percentage of CD3+ cells in the CD2+ lymphocyte preparations was significantly decreased in ATP patients relative to healthy controls (P < 0.05). But there was no significant correlation between this percentage and the blastogenic response to PHA in the CD2+ cellular preparations from both groups of subjects. No significant differences were found in the percentages of CD4+ and CD8+ cells. These data indicate that the impaired blastogenic response of T lymphocytes from ATP patients may be ascribed to an intrinsic defect in these T cells. This defective proliferative response of T lymphocytes from ATP patients cannot be ascribed to either defective interleukin 2 production or receptor expression which were both similar to those of healthy controls (P > 0.05). And, the presence of saturating amounts of exogenous interleukin 2 did not normalize the defective proliferative response the mitogenic signals on the part of T lymphocytes from ATP patients. We conclude that T lymphocytes from ATP patients have a defective proliferative response to membrane and intracytoplasmatic mitogenic signals.
Servicio de Hematologia, Hospital Principe de Asturias, Universidad de Alcala de Henares, Madrid, Spain.
J
J
Garcia-Suarez
A
A
Prieto
L
L
Manzano
E
E
Reyes
L
L
Molto
M
M
Alvarez-Mon
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D002469:Cell Separation / Q000379:methods; D002648:Child; D003593:Cytoplasm / Q000502:physiology / Q000648:ultrastructure; D004247:DNA / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000473:pathology* / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D017455:Receptors, IgE / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; D015375:Receptors, Interleukin-2; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D013936:Thymidine