QUANTITATIVE AND QUALITATIVE DIFFERENCES IN IL-2 AND IL-4 EXPRESSION IN PRIMARY AND SECONDARY T-CELL STIMULATION

Lymphocytes were concanavalin A (Con A) primed and the signal was withdrawn 4 - 48 h poststimulation by alpha-methyl-D-mannopyranoside (alpha-MM) treatment. Upon restimulation IL-2 and IL-4 RNA expression was found to be greatly enhanced. Re-expression of lymphokine RNA was dependent on signals delivered by Con A, anti-CD3 antibodies or phorbolester plus ionomycin, and could not be achieved by either IL-2, phorbolester or ionomycin alone. Increased IL-2 re-expression was only possible when alpha-MM was added early after primary stimulation, while the ability for enhanced IL-4 RNA re-expression persisted. IL-2 and IL-4 RNA re-expression was characterized by increases in steady state precursor RNA levels and thus, presumably, increased rates of transcription. However, the high accumulation of IL-2 RNA observed upon restimulation was also due to greatly increased RNA stability (> 4 h versus 30 min after primary stimulation). Thus, secondary expression of IL-4 RNA is persistent and mostly due to quantitative changes in transcription, whereas enhanced re-expression of IL-2 RNA also results from altered posttranscriptional regulation. This phenotype, however, is only short lived.