Partial inhibition of p38 MAPK reduces thymocyte number, suppresses thymocyte proliferation and IL-2 expression, and interferes with early thymocyte development.

(Panel A) Total thymocyte numbers from 11 pairs of 6-week-old NLC and lck-MKK3(A)/MKK6(A) transgenic mice. The thymocyte number of each pair is identified by the same symbol. The mean of each group is indicated next to the symbols. (Panel B) Proliferation of thymocytes from lck-MKK3(A)/MKK6(A) transgenic and NLC mice. The isolated thymocytes were activated with anti-CD3/anti-CD28, Con A (5 μg/mL), and TPA (10 ng/mL)/A23187 (80 ng/mL). The incorporation of thymidine was determined 60 hours later. (Panel C) IL-2 production of thymocytes from lck-MKK3(A)/MKK6(A) transgenic (Tg) and NLC mice. Thymocytes were stimulated with serially diluted Con A, and the IL-2 produced was quantitated 24 hours later using the IL-2–dependent cell line HT-2. Tg-(SP) indicates transgenic thymocytes analyzed with equal numbers of SP thymocytes as in NLC thymocytes. (Panel D) CD4⁻CD8⁻ thymocyte development was disturbed in MKK3(A)/6(A) transgenic mice. CD4⁻CD8⁻thymocytes from 6-week-old NLC, line-9, and line-2 transgenic mice were gated and analyzed for CD25 and CD44 expression. The number indicates the percentage of the subpopulation in CD4⁻CD8⁻ thymocytes. The SD is 15% of the mean value among 3 groups of mice with 4 mice in each group.