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Immune Responses in Multiple Sclerosis Patients Post T-Cell Vaccination

This study explores the immune responses post T-cell vaccination in multiple sclerosis patients, aiming to understand safety, clinical effects, and autoreactive T-cell mechanisms. It covers basic MS physiology, triggers, and common vocabulary related to antigens, antibodies, cytokines, and more. Materials and methods detail T-cell isolation, vaccination, and cytokine analysis processes. Results are recorded through stimulative indexes and cytokine production data. Figures demonstrate the proliferative responses post-vaccination and long-term cellular responses, highlighting the memory T-cell system within patients.

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Immune Responses in Multiple Sclerosis Patients Post T-Cell Vaccination

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  1. Multiple Sclerosis and the Immune ResponseBy: Terra McMillan Hermans, Guy, Ulrike Denzer, Ansgar Lohse, Jef Raus, and Piet Stinissen. 1999. Cellular and Humoral Immune Responses Against Autoreactive T cells in Multiple Sclerosis Patients After T cell Vaccination. Journal of Autoimmunity 13, 233-246.

  2. The Purpose • Study the safety, immune responses and clinical effects of T cell vaccination in 49 multiple sclerosis patients. • Gain insight on the mechanisms of autoreactive T cells

  3. What is Multiple Sclerosis? • Autoimmune disease • T cell mediated • ~250,000 people have MS • Women 2:1 ratio with men

  4. Basic Physiology of the Nervous System

  5. What triggers Multiple Sclerosis?

  6. Common Vocabulary • Antigen-A substance that cause the production of specific antibodies and combine with those antibodies. • Antibodies-Protein produced by the body to specifically react with a foreign substance • EAE- experimental autoimmune encephalomyelitis • Cytokines-Protein released in response to an antigen which influences other cells.

  7. Vocabulary Cont’d • PBMC-peripheral blood mononuclear cells • MBP-myelin basic protein • TCR-T cell receptor • CD markers-clusters of differentiation • MHC-major histocompatibility complex

  8. Materials and Methods • MBP reactive T cells were isolated from the peripheral blood and cloned • T cell clones was analyzed for TCR, rearrangements, and CDR3 sequence • Inactivation by irradiation • 49 MS patients were injected subcutaneously with 10x106 cells for T cell vaccination • 3 immunizations were performed at 2-month intervals

  9. Materials and Methods Cont’d. • Mononuclear cells isolated from blood samples and irradiated with T cell vaccine • Incubated for 4 days • Purified, label with radioactivity, and stored at –20oC for cytokine analysis • Results recorded in Stimulation Indexes (SI) • Net production of cytokine

  10. Materials and Methods Cont’d. • Patient serum Ig was bound to vaccine T cells using flow cytometry • Results were used in immunoblotting • Also patient serum was used to determine the proliferation of T cells

  11. Rationale for Figure 1. • The objective was to test if serum from vaccinated patients influenced the proliferation of T cells • PBMC of vaccinated patients were collected at various time intervals before and after vaccinations • Samples were irradiated with 3H-thymine

  12. Results- Proliferative Responses to T cell vaccines (y-axis= stimulation index)

  13. Conclusion-Figure 1. • All patients showed proliferative responses after vaccination, indicating an immune response • Proliferative responses often increased after the second and third vaccinations • Some clones were more effective than others

  14. Rationale-Figure 2. • Examination of long term proliferative responses using stimulation index • Samples all obtained after the third vaccination • Same irradiation procedures as for figure 1. were used • PHA blasts were used as the control

  15. Results-Long Term Proliferative Cellular Responses to T-cell Vaccinaation

  16. Conclusion-Figure 2. • SI’s gretaer than 2 were observed for all patiens at 1 and 2 years after vaccination • In some patients the response was greater than others • Indicates a memory T cell system within these patients

  17. Rationale-Figure 3. • Determining phenotypes of cytokines which responded to the vaccine clones • Short-term cell line cultures were obtained 3 weeks after vaccination 3 • Results were measured in SI units on the x-axis

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