Suppression of cytotoxic T-lymphocyte activation by pyruvate and L-alanine.
The activation of cytotoxic T lymphocytes (CTL) in allogeneic mixed-lymphocyte cultures was found to be strongly inhibited if 1-3 X 10(-2) M L-alanine or the structurally and biochemically related substance pyruvate was present in the period from 7 to 19 or from 19 to 120 hr. The cytotoxic response was not inhibited when L-alanine or pyruvate was present during the first 7 hr of the culture period. L-Alanine produced also little or no suppression, if added on Day 3 of the culture. L-Lactate or D-alanine at similar concentrations was not suppressive during the entire culture period. The suppression by pyruvate and L-alanine was strongly reduced by 1 X 10(-4) M adenosine. Adenosine in combination with an interleukin-2 (IL-2)-containing EL-4-cell supernatant was even more effective. Pyruvate and alanine (1-3 X 10(-2) M) also inhibited the DNA synthesis in mixed-lymphocyte cultures on Day 5 by about 50%, but both substances had practically no effect on DNA synthesis in cultures that had been supplemented with an IL-2-containing EL-4 supernatant. They had also no effect on the IL-2-dependent proliferation of several T-cell clones or of concanavalin A-activated thymocytes. These relatively selective regulatory effects of pyruvate and L-alanine may be useful for the analysis of the biochemical pathways during lymphocyte activation and/or for a selective manipulation of the immune response.
D000409:Alanine / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism
D011773:Pyruvates; D019289:Pyruvic Acid; D004247:DNA; D000409:Alanine