This report details the immunology of the first patient enrolled in the Canadian trial of immunoablative therapy with autologous stem cell transplantation (SCT) for MS. This trial tests the concept that immunoablative therapy can stop autoimmunity in MS and halt further CNS damage. Furthermore reconstitution of a naïve immune system should be functional and self-tolerant. A 31-yearold woman with secondary progressive MS underwent a CD34 selected autologous SCT after receiving Busulphan (16

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... ), Cyclophosphamide (200 mg/kg) and rabbit ATG (5 mg/kg). MS Activity: The patient is clinically stable 24 mo. post SCT with no relapses or progression of disabilities. There is sustained resolution of gadolinium activity and improved T2 metrics by MRI. Thus MS activity has been shut down. Immune ablation: The patient became lymphopenic. All lymphocyte subpopulations were decreased. There was loss of humoral immunity to mumps and measles at 18 mo. post SCT and lost cutaneous reactivity to candida at 6 and 12 mo. post SCT. Antigen specific in vitro T cell responses to myelin basic protein (MBP), tetanus toxoid (TT) and copaxone (GA) were reduced or abolished following SCT. There was Ͼ1000 fold reduction in recent thymic emigrants 3 mo. post SCT and a reduction in circulating naïve T cells. Thus immunoablation was achieved. Immune reconstitution: The patient has not developed opportunistic infections. The lymphocyte count has slowly risen during the post SCT period. Both helper and suppressor populations remain profoundly low with mainly a memory phenotype. The CD4:CD8 ratio normalized at 12 mo. post SCT. Thymic emigrants in the circulation have increased to about 10% of baseline. B cell and immunoglobulin levels are normal. Humoral immunity is polyclonal. A positive cutaneous response to candida antigen testing occurred 24 mo. post SCT. Specific in vitro T cell responses to TT following reimmunization are currently being evaluated. This preliminary data suggests that the post transplant immune system is protective and self-tolerant. The data from this patient indicates that complete immunoablation was achieved and is associated with a significant change in MS activity. The patient remains lymphopenic but is not prone to opportunistic infections. Immune reconstitution is ongoing and is NOT associated with recurrence of MS activity.