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p38 MAPK plays a role in IL-4 synthesis in jacalin plus CD28-stimulated CD4+ T cells--II
Seetha M Lakshmi Tamma1, Kun Wook Chung, Tejal Patel
1Department of Biomedical Sciences, C. W. Post Campus, Long Island University, 720 Northern Blvd., Brookville, NY 11548, USA. stamma@liu.edu
Insights
Jacalin and CD28 stimulation activate p38 MAPK in CD4+ T cells, promoting IL-4 secretion and anti-apoptotic protein expression. p38 MAPK inhibition blocks these effects, suggesting its crucial role in T cell activation and survival.
Area of Science:
- Immunology
- Cellular Signaling
Background:
- Jacalin, a CD4+ T cell lectin, induces intracellular phosphorylation and IL-2 secretion.
- CD28 costimulation with jacalin promotes IL-4 secretion.
- p38 MAPK is implicated in T cell activation pathways.
Purpose of the Study:
- To investigate the role of p38 MAPK in CD4+ T cell activation induced by jacalin and CD28 costimulation.
- To examine the effects of p38 MAPK inhibition on STAT-6, Bcl-2, and Bcl-xL expression.
- To differentiate the role of p38 MAPK in memory versus naïve T cells.
Main Methods:
- Stimulation of CD4+ T cells with jacalin and CD28 cross-linking (CD28XL).
- Inhibition of p38 MAPK using SB203580.
- Analysis of STAT-6 phosphorylation, Bcl-2 and Bcl-xL expression, and IL-4 secretion.
- Comparison between normal T cells, T cell blasts, memory T cells, and naïve T cells.
Main Results:
- Jacalin plus CD28XL induced STAT-6 phosphorylation and Bcl-2/Bcl-xL expression, inhibited by SB203580.
- CD28XL alone induced p38 MAPK phosphorylation and IL-4 secretion in memory T cells (jacalin blasts).
- p38 MAPK inhibition significantly reduced STAT-6, Bcl-2, and Bcl-xL expression, an effect not reversed by IL-4.
Conclusions:
- p38 MAPK plays a significant role in the induction of STAT-6, Bcl-2, and Bcl-xL during CD4+ T cell activation.
- p38 MAPK activation is critical for IL-4 secretion and expression of anti-apoptotic proteins.
- p38 MAPK may confer a survival advantage to activated T cells, protecting them from apoptosis.
Abstract:
We have previously shown that jacalin, a CD4+ T cell lectin, induces phosphorylation of intracellular events, moderate levels of interleukin (IL)-2 secretion. We have also shown that in the presence of CD28 costimulation, jacalin induces IL-4 secretion. In the present study, we showed that stimulation of normal CD4+ T cells with jacalin plus CD28 cross-linking (CD28XL) resulted in phosphorylation of signal transducer and activator of transcription (STAT)-6 and expression of Bcl-2 and Bcl-xL, which were inhibited significantly when cells were cultured in the presence of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. We further generated jacalin-induced CD4+ T cell blasts, examined the effects of CD28XL, and observed enhanced up-regulation of p38 and activation of STAT-6, Bcl-2, and Bcl-xL. Engagement of CD28 alone induced a marked degree of phosphorylation of p38 MAPK and IL-4 secretion in memory T cells (jacalin blasts), whereas in naïve T cells, jacalin plus CD28XL was required to induce these molecules. Incubation of cells with p38 inhibitor prior to CD28XL resulted in down-modulation of all these molecules. Further treatment with IL-4 has not reversed this trend. Our studies imply that p38 MAPK may play an important role in induction of these molecules and a putative role in protecting cells from undergoing apoptosis.
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