Identification of T-helper cells as the target of stearic acid-inhibition in primary antibody responses in vitro.
We have previously shown that albumin-complexed stearic acid (18:0) inhibited in vitro primary anti-TNP plaque-forming cell (PFC) responses to trinitrophenyl keyhole limpet hemocyanin (TNP-KLH), but did not affect primary PFC responses to trinitrophenyl lipopolysaccharide (TNP-LPS). The present studies were done to identify the cellular target of fatty acid inhibition. The addition of 18:0 at the initiation of antibody cultures exerted a dose-dependent inhibitory effect on subsequent PFC responses to TNP-KLH, and removal of the fatty acid after 20 h did not reverse its inhibitory effect. Preincubation of isolated T-cells with TNP-KLH and 18:0 resulted in a similar inhibition of subsequent PFC responses, but a preincubation of isolated B-cells had no effect. The addition of 18:0 to the culture system in vitro led to a marked reduction in the level of IL-2 detectable in culture supernatants, and PFC responses could be restored by providing exogenous mouse recombinant IL-2. The addition of antigen-primed T-helper cells to antibody cultures partially abrogated the inhibition by 150 microM 18:0, apparently due to their greater production of IL-2. Lastly, following overnight incubation of unfractionated splenic lymphocytes in the presence of TNP-KLH and [1-14C]-18:0, B-cells were shown to contain nearly 5-fold more radiolabeled oleic acid (18:1) than T-cells. Collectively, these findings implicate T-helper cells as the principle target of 18:0-inhibition of primary antibody responses in vitro, possibly as a result of the inability of T-helper cells to avoid an over accumulation of stearic acid in their membrane phospholipids.
Pourbohloul
S C
SC
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858-4354.
Buttke
T M
TM
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000378:metabolism; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013229:Stearic Acids / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology
D006241:Haptens; D007376:Interleukin-2; D013229:Stearic Acids; C054401:trinitrophenyl keyhole limpet hemocyanin; C031183:stearic acid; D006433:Hemocyanins