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Differential requirement of CD28 costimulation for activation of murine CD8+ intestinal intraepithelial lymphocyte
V Gelfanov1, Y G Lai, V Gelfanova
1Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, 2epublic of China.
Insights
Murine small intestinal intraepithelial lymphocytes (IELs) have two CD8+ subsets. Alpha beta-CD8+ IELs activate with TCR stimulation alone, while alpha alpha-CD8+ IELs show limited responses.
Area of Science:
- Immunology
- Gastrointestinal immunology
Background:
- Murine small intestinal intraepithelial lymphocytes (IELs) are crucial for gut immunity.
- CD8+ IELs comprise two distinct subpopulations: alpha alpha-CD8 and alpha beta-CD8 heterodimers.
- Understanding the activation requirements of these subsets is key to elucidating their immune functions.
Purpose of the Study:
- To investigate the differential activation requirements of alpha alpha-CD8+ and alpha beta-CD8+ IEL subsets.
- To compare the activation of CD8+ IELs with CD8+ lymph node (LN) cells.
Main Methods:
- Utilized plate-bound anti-TCR beta-chain (TCR-beta) monoclonal antibody (mAb) and anti-CD28 mAb for stimulation.
- Assessed proliferation, IL-2, and IFN-gamma production as indicators of activation.
- Investigated the effect of soluble CTLA-4 Ig on T cell responses.
Main Results:
- Alpha beta-CD8+ IELs proliferated and produced IL-2 and IFN-gamma upon TCR-beta stimulation alone.
- Alpha alpha-CD8+ IELs failed to proliferate or produce cytokines even with combined TCR-beta and CD28 stimulation.
- Both CD8+ IEL subsets exhibited lower proliferation capacity compared to CD8+ LN cells.
Conclusions:
- Alpha beta-CD8+ IELs possess distinct activation pathways compared to alpha alpha-CD8+ IELs and conventional T cells.
- The limited responsiveness of alpha alpha-CD8+ IELs may be due to intrinsic factors or a lower expression of co-stimulatory molecules.
- These findings highlight the specialized roles of CD8+ IEL subsets in intestinal immunity.
Abstract:
The CD8+CD4- (CD8+) murine small intestinal intraepithelial lymphocytes (IELs) contain two subpopulations, one expressing alpha alpha-CD8 homodimers and another alpha beta-CD8 heterodimers. In this study, plate-bound anti-TCR beta-chain (TCR-beta) mAb alone or combined with anti-CD28 mAb is used as a model system to study activation requirement of these two CD8+ IEL subsets. In contrast to CD8+ lymph node (LN) cells that require both TCR and CD28 triggering for activation, alpha beta-CD8+ IELs proliferate and produce IL-2 and IFN-gamma when stimulated with anti-TCR-beta mAb alone, and soluble CTLA-4 Ig has no effect on their responses. On the other hand, alpha alpha-CD8+ IELs neither make IL-2 or IFN-gamma nor proliferate even when both stimuli are provided. However, alpha alpha-CD8+ IELs are capable of proliferation in both CD8+ IEL subsets is lower than in CD8+ LN cells, which contributes to the weaker and delayed response of CD8+ IELs.