title: Aspirin-like drugs prime human T cells. Modulation of intracellular calcium concentrations.
abstract: Aspirin-like drugs (ALD) enhance T cell proliferation by suppressing PG production in monocytes. Normal human T cells do not produce any eicosanoids. Therefore we studied whether ALD would affect purified T cells directly. We found that ALD enhanced the proliferation and IL-2 production of T cells in the absence of monocytes. This effect did not depend on arachidonic acid metabolism as no lipoxygenase products and only nonsuppressive levels of cyclooxygenase products were detected in T cell cultures. Several possible mechanisms of the ALD effect were ruled out including 1) enhanced mitogen binding, 2) induction of activation markers (IL-2R, transferrin receptor, HLA-DR) on the cell surface, 3) down-regulation of suppressor cells. ALD caused a rise in [Ca2+]i which appeared to reflect an influx of Ca2+ from the extracellular milieu and was more pronounced in CD4+ cells. The rise in intracellular levels of Ca2+, that is considered a necessary second messenger for T cell activation, may prime these cells for an enhanced response to mitogens. In addition, ALD increased T cell membrane fluidity but only at higher concentrations than those found to enhance proliferation. The pharmacologic effect of ALD on T cells presents a possible new immunoenhancing potential of these drugs and may have therapeutic use in immunosuppressed individuals.
authors.affiliation: Clinical Immunology Section, Audie L. Murphy Memorial Veterans Hospital, San Antonio, TX.
authors.forename: E
authors.initials: E
authors.lastname: Flescher
authors.forename: D
authors.initials: D
authors.lastname: Fossum
authors.forename: P J
authors.initials: PJ
authors.lastname: Gray
authors.forename: G
authors.initials: G
authors.lastname: Fernandes
authors.forename: M J
authors.initials: MJ
authors.lastname: Harper
authors.forename: N
authors.initials: N
authors.lastname: Talal
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D016827:CD8 Antigens; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011863:Radioimmunoassay; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000945:Antigens, Differentiation, T-Lymphocyte; D001095:Arachidonic Acids; D016827:CD8 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D004008:Diclofenac; D016718:Arachidonic Acid; D005480:Flurbiprofen; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin