Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes

Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.

Determine the Effect of Immunosuppressant on follicular regulatory T-cells in kidney transplant patients

Background: Over the last few years, there are two major problems identified during organ transplantation such as surgical restrictions and transplant rejections. Few of these obstacles have been partially removed such as the use of immunosuppressant improved it consistently while decreasing graft rejection up to 12.2%. Methods: This study was conducted from 2019-2021. In all patients renal function was examined through glomerular filtration rate. Induction therapy was given to all the transplant recipients. Induction therapy with basiliximab 20mg intravenously on 0 and 4 days. After transplantation tacrolimus and MMF was given with varied concentration dose. Acute rejections were found in patients who had no biopsy or biopsy-proven rejection. In the end, clinical pathologists had analyzed all biopsies again and recipients who were experienced the vascular Banff grade 2 and tubule interstitial rejection. Results: Immunosuppressant tacrolimus treated patients were 71(67.61%) and mycophenolate mofetil used in 34(32.38%). Total 39(37.14%) rejections were received and 66(62.85%) acceptance was recorded. Two types of rejection were highlighted namely cell-mediated rejection 25(23.80%) and 14(13.33%) chronic antibody-mediated rejection. The effect of tacrolimus on follicular helper T cells and follicular regulatory T cells shows the clear difference between the kidney transplant and healthy control cells. Reduction in numbers of follicular regulatory T cells was measured in patients. Conclusion: eventually we find tacrolimus significantly affects the number of follicular regulatory T-cells and follicular helper T cells. Alemtuzumab substantially lowers the follicular regulatory T-cells. Mycophenolate mofetil showed non-significant on T-cells. Keywords: kidney transplant, follicular regulatory T-cells, follicular helper T-cells.