Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Neutralization of mitogenic lectins by intravenous immunoglobulin (IVIg) prevents T cell activation: does IVIg really have a direct effect on T cells?

“…However, we obtained evidence indicating that IVIg also interferes with the CD3/CD28 activation system, therefore preventing cell activation (L.P. and R.B., manuscript in preparation), rather than suppressing functions of activated T cells. Recent work from our laboratory using APCs to activate CD4 + T cells with immune complexes of ovalbumin revealed the absence of a direct effect of IVIg on T cell activation or proliferation [17]. Rather, our results showed that IVIg indirectly inhibited the in vivo and in vitro T cell responses by impairing antigen presentation.…”

“…More probably, the in vivo modulation of T cell populations observed in IVIg-treated patients is a consequence of the effect of IVIg on APCs [17]. Our work also emphasizes the importance of ruling out possible interactions of IVIg with mitogens or other effector components present in a given experimental system before deriving strong conclusions on the mechanisms of action of IVIg based on their apparent immunomodulatory effects observed in vitro.…”

“…However, a direct effect of IVIg on T cells was questioned following reports from Achiron et al [15] and Skanse-Saphir et al [16]. In addition, work from our laboratory has established recently that IVIg has no direct effect on antigen-activated T cells, but rather modulates the functions of antigen-specific T cells by reducing the activity of antigen-presenting cells (APCs) [17]. These recent observations on the absence of a direct effect of IVIg on T cells prompted us to re-examine the mechanisms by which IVIg interfered with the functions of T cells activated with lectins.…”

Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2–dependent prostaglandin E2 in human dendritic cells

“…[15][16][17][18][19][20][21][22][23][24][25][26] However, the cellular and molecular mechanisms by which IVIg expands Tregs are relatively unknown. As Treg expansion in the periphery requires signaling by antigen-presenting cells such as dendritic cells (DCs) 27,28 and IVIg has been demonstrated to modulate DC functions, [29][30][31][32] we hypothesized that IVIg induces distinct signaling events in DCs. These IVIg-educated DCs subsequently mediate the expansion of Tregs.…”

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

“…Cord blood units were obtained from the CHU Sainte-Justine Research Cord Blood Bank following approval by the ethics committee. Mice were injected intravenously with 10 5 hCD34 þ cells following 3 Gy sub-lethal irradiation and treated with either PBS or IVIG (Gamunex 50 mg/mouse) 23,24 once a week from day À1 until the end of the experiment. Engraftment and immune reconstitution were assessed weekly on blood samples by flow cytometry.…”