Inhibition of lymphocyte proliferation by free fatty acids. III. Modulation of thymus-dependent immune responses.
Free fatty acids (FFA) were tested for their effects on in vitro thymus-dependent (TD) and thymus-independent (TI) immune responses. Murine T cells proliferating in one-way mixed leucocyte reactions (MLR) were extremely sensitive to inhibition by exogenous stearic acid (18:0) but were only moderately affected by oleic acid (18:1). T-cell proliferation was suppressed when 18:0 was added as late as 44 hr after allogeneic stimulation, but sensitivity to 18:1 was limited to the first 30 hr of culture. The inhibitory effects of 18:0, but not 18:1 were potentiated by concomitant T-cell activation and under such conditions the effects of 18:0 were irreversible within 5 hr. The two fatty acids were additionally tested for their effects on the anti-hapten antibody-secreting cell responses to TD and TI antigens. Both 18:0 and 18:1 inhibited the primary antibody response elicited by a TD antigen (TNP-KLH) but neither fatty acid significantly affected the primary antibody response to a TI antigen (TNP-LPS). Following in vivo immunization with TNP-KLH, isolated spleen cells were challenged with the same antigen in vitro in the presence of FFA. Whereas 18:1 had little effect on the secondary immune response, the addition of 18:0 led to a 3-4-fold increase in the number of anti-TNP plaque forming cells. Further studies showed that TNP-KLH-induced T cell proliferation was potently inhibited by 18:0 but 18:1 had no effect. These results suggest that an inhibition of T-cell proliferation is the primary way in which 18:0 modulates TD immune responses in vitro. By contrast, 18:1 appears to inhibit primary antibody responses and MLR via alternative mechanisms.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000941:Antigens / Q000276:immunology; D004247:DNA / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D006462:Hemolytic Plaque Technique; D007156:Immunologic Memory / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects; D009829:Oleic Acids / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000941:Antigens; D005230:Fatty Acids, Nonesterified; D008070:Lipopolysaccharides; D009829:Oleic Acids; D013229:Stearic Acids; D004247:DNA