Role of reentry of in vivo alloMHC peptide-activated T cells into the adult thymus in acquired systemic tolerance.

BACKGROUND: T cell recognition of alloMHC peptide presented by self dendritic cells via the indirect pathway of allorecognition in the thymus induces T cell tolerance. Most recently we have shown that the i.v. administration of immunodominant Wistar Furth MHC class I (RT1.Au) peptide 5- (P5) pulsed myeloid or lymphoid dendritic cells induces operational tolerance to a fully MHC-mismatched cardiac allograft. This finding led us to hypothesize that circulation of peripheral P5-activated T cells to the thymus plays an important role in the induction of acquired tolerance. METHODS: We used the adoptive transfer of 111Indium-oxine- (111In-oxine) labeled P5-pulsed syngeneic dendritic cells and in vivo P5-activated syngeneic T cells to study the role of their circulation to the thymus in the induction of transplantation tolerance. RESULTS: Intravenously administered 111In-oxine-labeled naïve DC actively migrated to and localized in the liver and spleen but did not enter the lymph nodes, bone marrow, and thymus. In vitro peptide-pulsed dendritic cells had a similar pattern of tissue localization except for a modest number of myeloid but not lymphoid DC entering the thymus. The demonstration that adoptive transfer of in vivo peptide-primed T cells induces permanent graft survival in antilymphocyte serum transiently immunosuppressed syngeneic secondary hosts led us to examine the traffic of in vivo activated T cells. Whereas naïve syngeneic T cells preferentially homed to the peripheral lymphoid organs, they did not reenter the thymus. In contrast, in vivo peptide-activated peripheral T cells migrated to and accumulated in the thymus, thus confirming that reentry of T cells to the thymus is restricted to in vivo activated T cells. Although antilymphocyte serum immunosuppression significantly reduced circulation of primed T cells to the thymus, it did not completely abolish it, as seen with gamma-irradiated primed T cells. CONCLUSION: These findings provide the first formal evidence directly linking reentry of in vivo alloMHC peptide-activated T cells to the thymus with the induction and possibly maintenance of acquired antigen-specific tolerance. Our results suggest that the thymus is open to a two-way traffic with the periphery and may function as a repository of immunological memory.

Basilar artery stenosis: clinical and neuroradiographic features.

INTRODUCTION: Although basilar artery stenosis (BAS) is an important cause of posterior circulation stroke, few reports detail the clinical and neuroradiological features of patients with BAS. METHODS: A retrospective review of symptomatic BAS patients who were evaluated by our Stroke Center. RESULTS: Twenty-eight patients were followed-up for a median of 16 months. Transient ischemic attacks (TIAs) specific for posterior circulation involvement were common (12/19 patients with TIA), were often multiple, and frequently preceded a posterior circulation stroke. The proximal (13/28) and mid (10/28) basilar arteries were the most common sites of stenosis. Brain infarction most often affected the pons, but also frequently involved the cerebellum and thalamus. Concomitant vertebral artery disease was prevalent (12/18 patients who underwent conventional cerebral angiography). Stroke mechanisms included artery to artery embolus, basilar branch disease, and hypoperfusion. The same-territory recurrent stroke rate was 8.2% per year. Most patients in the series were treated with warfarin. No patients suffered a recurrent stroke while on a therapeutic dose of warfarin (international normalized ratio [INR], 2.0 to 3.0). Angioplasty was performed in 6 patients. CONCLUSIONS: The same-territory stroke recurrence rate was 8.2% per year. Warfarin (INR, 2.0 to 3.0) appeared to be effective in preventing recurrent strokes. Angioplasty of the basilar artery was technically feasible. Symptomatic BAS typically affected the proximal and mid-basilar artery and most often caused infarction in the pons. The mechanisms for stroke were heterogeneous. TIAs frequently preceded a posterior circulation stroke.

Angiographically defined primary angiitis of the CNS: is it really benign?

BACKGROUND: Primary angiitis of the CNS (PACNS) is a diagnostically challenging disorder. In patients whose diagnosis is ascertained solely by cerebral angiography without histologic verification, a benign monophasic clinical course with favorable response to a brief course of immunosuppressive therapy is often reported. METHODS: We performed a retrospective review of patients with PACNS seen at the Stanford Stroke Center. RESULTS: Patients were followed for a median of 27.5 months. Acute focal deficits (9 of 10) and headache (3 of 10) were the most frequent presenting symptoms. Significant recurrent neurologic symptoms occurred in 5 of 10 patients before the initiation of immunosuppressive treatment. Three of six patients had recurrent symptoms during prednisone therapy alone, whereas only one of seven patients had recurrent symptoms while receiving combination immunosuppressive therapy. None had recurrent stroke during immunosuppressive treatment. Dynamic arterial changes were seen in four of five patients who underwent follow-up angiography that often, but not always, correlated with disease activity. CONCLUSIONS: Patients with angiographically defined PACNS frequently did not have a benign outcome or monophasic course. Repeat angiography was useful in supporting the diagnosis of PACNS, but did not always correlate with disease activity. A prospective multicenter collaborative effort is required to better define the clinical course and optimal treatment of PACNS.

Triterpenoid saponins from the root of Sideroxylon cubense.

Two triterpenoid saponins were isolated from the root of Sideroxylon cubense and their structures were established as 3-O-beta-D-glucopyranosyl-28-O-[alpha-L-rhamnopyranosyl(1-->3)- beta-D-xylopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->2) beta-D-xylopyranosyl] protobassic acid and 3-O-beta-D-glucopyranosyl protobassic acid. The first, designed as sideroxyloside A, is a new natural product.