Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement

Linsley, Peter S.; Bradshaw, Jeff; Greene, JoAnne L.; Peach, Robert; Bennett, Kelly L.; Mittler, Robert S.

doi:10.1016/s1074-7613(00)80480-x

Cited by 542 publications

(435 citation statements)

References 27 publications

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“…A decreased CTLA-4 expression level was previously described in activated cells [21,22], and it is known that CTLA-4 is essential for initial Treg in vivo suppressor activity on APCs [23,24]. According to our results, we suggest that rapid CTLA-4 internalization occurs in Tregs at the moment of contact with APCs, suppressing the expression of MHC II and/or B7 molecules on the later.…”

Section: Discussionsupporting

confidence: 81%

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Silva

Caetano

Monteiro

et al. 2012

Cellular Immunology

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a b s t r a c tAlthough the role of regulatory T cells (Tregs) during malaria infection has been studied extensively, such studies have focused exclusively on the role of Treg during the blood stage of infection; little is known about the detailed mechanisms of Tregs and sporozoite deposition in the dermis by mosquito bites. In this paper we show that sporozoites introduced into the skin by mosquito bites increase the mobility of skin Tregs and dendritic cells (DCs). We also show differences in MHC class II and/or CD86 expression on skin-resident dendritic cell subtypes and macrophages. From the observed decrease of the number of APCs into draining lymph nodes, suppression of CD28 expression in conventional CD4 T cells, and a low homeostatic proliferation of skin-migrated CD4 T found in nude mice indicate that Tregs may play a fundamental role during the initial phase of malaria parasite inoculation into the mammalian host.

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Section: Discussionsupporting

confidence: 81%

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Silva

Caetano

Monteiro

et al. 2012

Cellular Immunology

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“…Our data on IFN-␥R2 internalization were obtained with divalent mAb, which can give rise to patching and capping induced by ligand multivalency (20). Although we did not use monovalent Fab fragments to avoid this problem, recycling of IFN-␥R2 was confirmed by additional data.…”

Section: Effect Of Endogenous Ifn-␥ On Ifn-␥r2 Internalization In Tmentioning

confidence: 82%

“…4A, lower panels). CTLA-4 is a low expressed surface receptor involved in the inhibition of T cell functions (19) and recycles between the membrane and the cytoplasm (20). A time-dependent uptake of C.11 and anti-CTLA-4 mAb was evident at 37°C only (not shown).…”

Section: Cycling Of Ifn-␥r2 Between Cytoplasmic Stores and The Cell Smentioning

confidence: 93%

Surface Expression of the IFN-γR2 Chain Is Regulated by Intracellular Trafficking in Human T Lymphocytes

Rigamonti

Ariotti

Losana

et al. 2000

The Journal of Immunology

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The surface and cytoplasmic expressions of the transducing chain (IFN-γR2) of the heterodimeric IFN-γ receptor on human T lymphocytes have been investigated. We show that its surface expression is low, whereas high cytoplasmic levels are found in both resting and PHA-activated T lymphocytes. This low expression does not prevent activated T cells from responding to IFN-γ, because it induces IFN-regulatory factor 1 expression. Low surface IFN-γR2 expression appears to be due to recycling between cytoplasmic stores and the cell surface, which does not depend on signals mediated by endogenous IFN-γ, because IFN-γR2 surface expression is low, and its internalization is equally observed in patients with inherited IFN-γR1 gene deficiency and in healthy donors. Moreover, IFN-γR2 internalization in T lymphoblasts from healthy donors was not affected by the presence of anti-IFN-γ-neutralizing or anti-IFN-γR1-blocking mAb. In conclusion, these data illustrate a new mechanism whereby human T cells limit the surface expression of IFN-γR2 in a ligand-independent manner.

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“…It is of note that the HP-F1 mAb, that in our experiments was the most efficient mAb in functional assays, was able to exert inhibition also in HP-F1 surfaceϪ clones. There are two possible explanations for this finding: 1) surface immunofluorescence is less sensitive when compared with the functional assays, and thus a lower number of molecules is sufficient to determine inhibition; 2) similarly to that observed for CD152, a redistribution from the cytoplasm to the membrane may occur in the course of the functional assays (27).…”

Section: Different Degree Of Inhibition Of Cd3-induced Proliferatiomentioning

confidence: 95%

The CD85/LIR-1/ILT2 Inhibitory Receptor Is Expressed by All Human T Lymphocytes and Down-Regulates Their Functions

Saverino

Fabbi²,

Ghiotto

et al. 2000

The Journal of Immunology

133

128

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The inhibitory molecule CD85/LIR-1/ILT2 has been detected previously on the surface of a small proportion of T lymphocytes. In this study, evidence is provided that, although only a fraction of CD3+ cells are stained by mAb specific for CD85/LIR-1/ILT2 on their surface, this inhibitory receptor is present in the cytoplasm of all T lymphocytes, and that it is detectable on the surface of all T cell clones by the M402 mAb. Biochemical analyses further demonstrate that CD85/LIR-1/ILT2 is present in all T clones analyzed, and that the protein is tyrosine-phosphorylated. Expression of mRNA coding for CD85/LIR-1/ILT2 has been assessed by RT-PCR. Notably, in the NKL cell line and in one T cell clone, amplification of the messenger required 30 cycles only, whereas, in other T cell clones, an amplification product was detected by increasing the number of cycles. CD85/LIR-1/ILT2 inhibits CD3/TCR-mediated activation in both CD4+ and CD8+ clones, and it down-regulates Ag recognition by CD8+ cells in a clonally distributed fashion. Addition of anti-ILT2 HP-F1 mAb in the cytolytic assay enhances target cell lysis mediated by Ag-specific CTL. This could be due to interference of the mAb with receptor/ligand interactions. In contrast, HP-F1 mAb cross-linking triggers inhibitory signals that reduce cytotoxicity. CD85/LIR-1/ILT2 also controls responses to recall Ags and, in low responders, its engagement sharply increases T cell proliferation. The inhibitory function of the molecule is also confirmed by its ability to reduce CD3/TCR-induced intracellular Ca2+ mobilization.

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Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement

Cited by 542 publications

References 27 publications

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Surface Expression of the IFN-γR2 Chain Is Regulated by Intracellular Trafficking in Human T Lymphocytes

The CD85/LIR-1/ILT2 Inhibitory Receptor Is Expressed by All Human T Lymphocytes and Down-Regulates Their Functions

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