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CD2-SLFA3/T11TS interaction facilitates immune activation and glioma regression by apoptosis
Susobhan Sarkar1, Anirban Ghosh, Joydeep Mukherjee
1Cellular and Molecular Immunology Lab, Department of Physiology, Dr. B.C. Roy Institute of Basic Medical Sciences, Institute of Post Graduate Medical Education and Research (IPGME&R) Kolkata 700020, India.
Objective:
Exogenous application of T11TS/SLFA3 in glioma model had shown the regression of tumor load through immunopotentiation. The mechanistic module of this interaction on immunological synapse formation and resulting effect in glioma regression is searched for delineating immunotherapeutic efficacy of T11TS.
Methods:
After purification of T11TS/SLFA3 from sheep erythrocytes the glycoprotein was characterized by SDS-PAGE analysis and glycoprotein staining. The modulatory effect of T11TS application on glioma animals were studied by CD2 and MHC class II expression on peripheral lymphocytes, PMN, macrophages and intracranial microglia by flowcytometric analysis. Finally apoptotic killing of brain cells were studied through annevin-V expression and measuring fragmented cytoplasmic DNA by ELISA.
Results:
Compared to healthy normal counter-parts the CD2 receptor downregulation by ENU treatment in lymphocytes and PMN were upregulated with three consecutive doses of T11TS. Splenic antigen presenting macrophages and intracranial mocroglia had shown CD2 and MHC class II modulation simultaneously in their different subtypes. These receptor studies revealed significant boosting of the immune competent cells most effectively in second dose of T11TS whereas the third dose had some regulatory effect. Sharp increase of apoptosis in brain cells was found by phosphatidylserine externalization and presence of fragmented DNA in cytoplasm with application of T11TS in consecutive doses as a result of immune potentiation.
Conclusion:
Receptor studies revealed modulation of CD2 and MHC class II, two important constituents of immunological synapse successfully help to form the TCR-p-MHC complex and provide required co-stimulation for activation. Potentiated immune effector machinery was then directed to abrogate glioma by apoptosis signifying T11TS as an immunotherapeutic probe.
Insights
T11TS/SLFA3 immunotherapy boosts immune cells, enhancing T-cell receptor-peptide-MHC complex formation and co-stimulation. This potentiated immune response effectively eliminates glioma cells through apoptosis, demonstrating T11TS as a promising immunotherapeutic agent.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Glioma progression is often associated with immune evasion.
- T11TS/SLFA3, a glycoprotein from sheep erythrocytes, has shown potential in reducing glioma tumor load via immune potentiation.
- Understanding the precise mechanisms of T11TS/SLFA3 in modulating the immune response within the glioma microenvironment is crucial for its therapeutic development.
Purpose of the Study:
- To investigate the mechanistic effects of T11TS/SLFA3 on immunological synapse formation in a glioma model.
- To delineate the immunotherapeutic efficacy of T11TS/SLFA3 in promoting glioma regression.
- To characterize the expression of CD2 and MHC class II molecules and their role in immune cell activation.
Main Methods:
- Purified T11TS/SLFA3 glycoprotein was characterized using SDS-PAGE and glycoprotein staining.
- Flow cytometry was employed to analyze CD2 and MHC class II expression on lymphocytes, PMNs, macrophages, and microglia in glioma-bearing animals treated with T11TS/SLFA3.
- Apoptosis in brain cells was assessed by measuring Annexin-V expression and quantifying fragmented cytoplasmic DNA via ELISA.
Main Results:
- T11TS/SLFA3 treatment upregulated CD2 receptor expression on lymphocytes and PMNs, counteracting ENU-induced downregulation.
- Both splenic antigen-presenting macrophages and intracranial microglia exhibited simultaneous modulation of CD2 and MHC class II expression across different subtypes.
- Significant boosting of immune cells was observed, with the second dose of T11TS/SLFA3 being most effective, while a third dose showed a regulatory effect.
- A marked increase in glioma cell apoptosis was detected, evidenced by phosphatidylserine externalization and fragmented DNA, following T11TS/SLFA3 administration.
Conclusions:
- T11TS/SLFA3 effectively modulates CD2 and MHC class II, key components of the immunological synapse.
- This modulation facilitates the formation of the T-cell receptor-peptide-MHC complex and provides essential co-stimulation for immune cell activation.
- The resulting potentiated immune response effectively targets and eliminates glioma cells through apoptosis, establishing T11TS/SLFA3 as a viable immunotherapeutic agent for glioma.
