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Real-time Live Imaging of T-cell Signaling Complex Formation
Published on: June 23, 2013
Activation and signaling status of human lamina propria T lymphocytes
L Qiao1, G Schürmann, M Betzler
1Department of Applied Immunology, German Cancer Research Center, Heidelberg.
Insights
Human lamina propria T lymphocytes show reduced proliferation to T-cell receptor stimulation due to intestinal factors. Alternative activation pathways via CD2 and CD28 remain functional, potentially aiding gut T-B cell interactions.
Area of Science:
- Immunology
- Gastrointestinal Biology
Background:
- Lamina propria T lymphocytes (LPLs) are crucial for gut immunity.
- Understanding LPL activation is key to gut immune regulation.
Purpose of the Study:
- To investigate the proliferative responses and activation pathways of human LPLs in vitro.
- To identify factors within the intestinal mucosa that influence LPL reactivity.
Main Methods:
- In vitro analysis of human LPL proliferative responses.
- Stimulation using anti-CD3, anti-T11(2/3), and anti-CD28 antibodies.
- Measurement of intracellular signaling molecules (inositol 1,4,5-triphosphate, calcium).
- Coculture experiments with mucosal supernatant.
Main Results:
- LPLs exhibited significantly lower proliferation to T-cell receptor (TCR) stimulation (anti-CD3) compared to peripheral blood T lymphocytes.
- Responses to alternative activation pathways (anti-T11(2/3), anti-CD28) were preserved in LPLs.
- Reduced TCR responsiveness correlated with impaired intracellular signaling (inositol 1,4,5-triphosphate and calcium flux).
- Peripheral blood T lymphocytes showed similar hyporesponsiveness after exposure to mucosal supernatant.
Conclusions:
- Intestinal mucosal factors down-regulate the TCR-dependent activation pathway for LPL proliferation.
- Alternative activation pathways (CD2, CD28) are largely preserved in LPLs.
- These preserved pathways may be critical for T-B cell interactions within the gut immune system.
Abstract:
In this study, proliferative responses of human lamina propria T lymphocytes were examined in vitro. The response of lamina propria T lymphocytes to Sepharose-bound anti-CD3 antibody plus interleukin 2 was significantly lower than the response of autologous peripheral blood T lymphocytes, whereas the responses of lamina propria T lymphocytes to anti-T11(2/3) antibodies plus sheep erythrocytes or anti-CD28 antibody plus interleukin 2 were largely preserved. After coculture with mucosa supernatant, peripheral blood T lymphocytes showed a similar pattern of reactivity as lamina propria T lymphocytes. This reduced reactivity to T-cell antigen receptor stimulation appears to exist at the level of signal transduction, because triggering of CD3 induces low amounts of intracellular inositol 1,4,5-triphosphate and no free calcium increase in lamina propria T lymphocytes when compared with peripheral blood T lymphocytes. This study indicates that the antigen receptor-dependent activation pathway of lamina propria T lymphocytes for proliferation is down-regulated by intestinal mucosa derived factor(s) and that the alternative pathways mediated by CD2 or CD28 are largely preserved. Based on previous data that lamina propria T lymphocytes can provide help to B cells, it is possible that these alternative activation pathways play an important role in T-B cell interaction in the gut.
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