IgG from atopic individuals can mediate non atopic infant thymic and adult peripheral CD8 TC2 skewing without influence on TC17 or TC22 cells

Abstract

The potential of IgG antibodies as allergy regulators has been discussed for decades and was brought to light that anti-allergen IgG is related to allergy inhibition in children during the first years of life and that IgG repertoire can differ between atopic and non-atopic individuals. Here, we aimed to evaluate in vitro the differential effects of purified IgG from atopic and non-atopic individuals on the production of IL-4, IL-17, and IL-22 by human intra-thymic and mature peripheral CD8 + T cells respectively termed as TC2, TC17, and TC22 cells. We additionally evaluated the IFN-γ production by CD8 + T cells. Thereupon we used infants thymic tissues from non-atopic mothers and blood samples from individuals clinically classified as non-atopic. Thymocytes or PBMCs were cultured with IgG from atopic or non-atopic individuals. As controls, we used commercial IgG (Intravenous immunoglobulin -IVIg) or mock condition. The phenotype and intracellular cytokine production were evaluated using flow cytometry. IgG from atopic individuals could increase the frequency of TC2 cells in non-atopic infant thymic and adult peripheral cell cultures compared to all control conditions. Due to the TC2 cell's potential to collaborate with pathology and severity of asthma in humans, this evidence can cooperate with the understanding of the development of an atopic state.

Immune modulation and possible pathological implications mediated by naturally produced immunoglobulin G idiotypes: from historical to recent experimental and clinical studies focused on atopic dermatitis

“…Some in vitro studies have also demonstrated that atopic IgG repertoire can modulate CD8+ T cell functions. Recently, it was shown that IgG from atopic individuals could induce non-atopic infant thymic and adult peripheral CD8+ T cells to produce IL-4, acquiring a TC2 profile [ 30 ]. However, this study did not investigate if this effect was mediated by the direct interaction of IgG with CD8+ T cell membrane, not even TCRs.…”

Non-atopic Neonatal Thymic Innate Lymphoid Cell Subsets (ILC1, ILC2, and ILC3) Identification and the Modulatory Effect of IgG From Dermatophagoides Pteronyssinus (Derp)-Atopic Individuals

“…In the last 24 h, 10 µg/mL Brefeldin A (Sigma, Israel) was added only to the wells dedicated to evaluating intracellular cytokine production. This protocol was previously standardized using positive (Phorbol 12-myristate 13-acetate-PMA) and negative controls (mock condition), and due to the absence of polyclonal stimulation, we could maintain Brefeldin A for 24 h without decreasing cell viability (32,34,35,37,38,42).…”

“…Previous studies in the literature demonstrated that IgG antibodies could interact with lymphocytes precursors in the murine and human thymus, modulating its cytokine production as recently revised ( 31 ). Together, these pieces of evidence suggest that atopic and non-atopic individuals' IgG repertoire can differentially modulate the maturation of thymic TCD4, TCD8, iNKT B, and γδT cells modulating or inhibiting the development of allergy ( 32 – 42 ). In those observations, it has become evident that IgG antibodies can interact with a wide range of clonal or conserved receptors expressed in several cell populations.…”

IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction

“…Recently, the "hooks without bait" immunological hypothesis proposed that polyclonal IgG repertoires from different donor groups may play essential roles in modulating the function of thymic and peripheral T and B cells 16 . In this context, polyclonal IgG from individuals with allergies, atopic dermatitis, HIV infection, and HTLV infection has demonstrated in vitro modulatory effects on various thymic and peripheral lymphocytes, including T cells, B cells, γδT cells, iNKT cells, and innate-like cells (ILC) in both humans and mice 17 – 25 . These effects have the potential to modulate the pathophysiology of these diseases.…”