NDLI: Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses

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Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses

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Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Puliaeva, Irina Puliaev, Roman Haas, Mark Via, Charles S. Shustov, Andrei
Description	Country affiliation: United States Author Affiliation: Puliaeva I ( Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.)
Abstract	Fas-mediated apoptosis is an important contributor to contraction of Ag-driven T cell responses acting only on activated Ag-specific T cells. The effects of targeted Fas deletion on selected cell populations are well described however little is known regarding the consequences of Fas deletion on only activated Ag-specific T cells. We addressed this question using the parent-into-F(1) (P-->F(1)) model of acute or chronic (lupus-like) graft-vs-host disease (GVHD) as a model of either a CTL-mediated or T-dependent B cell-mediated response, respectively. By transferring Fas-deficient lpr donor T cells into Fas-intact F(1) hosts, the in vivo role of Ag-specific T cell Fas can be determined. Our results demonstrate a novel dichotomy of Ag-specific T cell Fas function in that: 1) Fas expression on Ag-activated T cells has costimulatory, helper, and down-regulatory roles in vivo and 2) these roles were observed only in a CTL response (acute GVHD) and not in a T-dependent B cell response (chronic GVHD). Specifically, CD4 T cell Fas expression is important for optimal CD4 initial expansion and absolutely required for help for CD8 effector CTL. Donor CD8 T cell Fas expression played an important but not exclusive role in apoptosis and down-regulation. By contrast, CD4 Fas expression played no detectable role in modulating chronic GVHD induction or disease expression. These results demonstrate a novel role for Ag-specific T cell Fas expression in in vivo CTL responses and support a review of the paradigm by which Fas deficiency accelerates lupus in MRL/lpr lupus-prone mice.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd95 Biosynthesis B-lymphocytes Immunology Cd4-positive T-lymphocytes Down-regulation Epitopes, T-lymphocyte Lymphocyte Activation T-lymphocytes, Cytotoxic T-lymphocytes, Helper-inducer Acute Disease Animals Genetics Physiology Metabolism Transplantation Cell Line, Tumor Cells, Cultured Crosses, Genetic Administration & Dosage Graft Vs Host Disease Mortality Lupus Nephritis Pathology Mice Mice, Inbred C57bl Mice, Inbred Mrl Lpr Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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IL-21 receptor is required for the systemic accumulation of activated B and T lymphocytes in MRL/MpJ-Fas(lpr/lpr)/J mice.

Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice.

Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses1

CXCL13 blockade attenuates lupus nephritis of MRL/lpr mice.

Induction of rapid T cell death and phagocytic activity by Fas-deficient lpr macrophages.

B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice.

Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation.

T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells.

B cell-derived IL-10 does not regulate spontaneous systemic autoimmunity in MRL.Fas(lpr) mice.

Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses

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IL-21 receptor is required for the systemic accumulation of activated B and T lymphocytes in MRL/MpJ-Fas(lpr/lpr)/J mice.

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Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses1

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Fas expression on antigen-specific T cells has costimulatory, helper and downregulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses