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

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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

Barcenilla, Hugo (author): Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten

Pihl, Mikael (author): Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten

Wahlberg, Jeanette, 1969- (author): Linköpings universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Health, Medicine and Caring Sciences (HMV), Linköping University, Linköping, Sweden; Division of Diagnostics and Specialist Medicine and Faculty of Health Sciences, Örebro University, Örebro, Sweden,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Endokrinmedicinska kliniken,Orebro Univ, Sweden; Orebro Univ, Sweden

Ludvigsson, Johnny (author): Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus

Casas, Rosaura (author): Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten

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2022-01-12
2021
English.
In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12

Related links:: https://doi.org/10.3...; show more...; https://www.frontier...; https://liu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.3...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

B cell response
GAD-alum
T cell exhaustion
T1D
antigen-specific immunotherapy
follicular T helper cells
mass cytometry (CyTOF)
type 1 diabetes

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art (subject category)

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By the author/editor: Barcenilla, Hugo; Pihl, Mikael; Wahlberg, Jeanet ...; Ludvigsson, John ...; Casas, Rosaura

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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By the university: Örebro University; Linköping University

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