Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells

CTLA-4 has been proposed to negatively regulate immune responses, and mice deficient for CTLA-4 expression succumb to a lymphoproliferative disorder within a few weeks after birth. This study assessed the responsiveness of CTLA-4-deficient T cells expressing a class I-restricted TCR specific for lym...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 1998-01, Vol.160 (1), p.95-100
Main Authors: Bachmann, M F, Waterhouse, P, Speiser, D E, McKall-Faienza, K, Mak, T W, Ohashi, P S
Format: Article
Language:English
Subjects:
Abatacept
AIDS/HIV
Amino Acid Sequence
Animals
Antigens, CD
Antigens, Differentiation - physiology
CD8-Positive T-Lymphocytes - immunology
CTLA-4 Antigen
Immunoconjugates
Lymphocytic Choriomeningitis - immunology
Mice
Mice, Knockout
Mice, Transgenic
Peptides - immunology
T-Lymphocytes, Cytotoxic - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:CTLA-4 has been proposed to negatively regulate immune responses, and mice deficient for CTLA-4 expression succumb to a lymphoproliferative disorder within a few weeks after birth. This study assessed the responsiveness of CTLA-4-deficient T cells expressing a class I-restricted TCR specific for lymphocytic choriomeningitis virus (LCMV). The kinetics of T cell proliferation were studied in vitro after stimulation of T cells with full and partial T cell agonists. No gross abnormalities in CTLA-4-deficient T cells could be detected. Using adoptive transfer experiments, T cell responses were also measured in vivo after infection with LCMV. Low dose infection with LCMV leads to strong expansion of specific T cells followed by a reduction in T cells that parallels the elimination of Ag. The kinetics of T cell expansion and elimination after low dose LCMV infection were not affected by the absence of CTLA-4. High dose infection of mice with LCMV leads to a transient expansion of T cells followed by T cell exhaustion, where all specific T cells are eliminated. T cell exhaustion also occurred in the absence of CTLA-4. Thus, surprisingly, the absence of CTLA-4 did not interfere with T cell activation, down-regulation of ongoing T cell responses after the elimination of Ag, or the exhaustion of T cell responses in the presence of excessive amounts of Ag.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.1.95