Abstract
CTLA-4-deficient animals develop a fatal lymphoproliferative disorder. The cellular mechanism(s) responsible for this phenotype have not been determined. Here, we show that there is a preferential expansion of CD4+ T cells in CTLA-4(-/-) mice, which results in a skewing of the CD4/CD8 T cell ratio. In vivo antibody depletion of CD8+ T cells from birth does not alter the onset or the severity of the CD28-dependent lymphoproliferative disorder. In contrast, CD4+ T cell depletion completely prevents all features characteristic of the lymphoproliferation observed in CTLA-4-deficient mice. These results demonstrate that CD4+ T cells initiate the phenotype in the CTLA-4(-/-) mice. Further, these results suggest that the role of CTLA-4 in peripheral CD4+ versus CD8+ T cell homeostasis is distinct.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Abatacept
-
Animals
-
Antigens, CD
-
Antigens, Differentiation / genetics
-
Antigens, Differentiation / immunology*
-
B-Lymphocytes / cytology
-
B-Lymphocytes / immunology
-
B7-1 Antigen / immunology
-
CD28 Antigens / immunology
-
CD4-CD8 Ratio
-
CD4-Positive T-Lymphocytes / cytology
-
CD4-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / cytology
-
CD8-Positive T-Lymphocytes / immunology
-
CTLA-4 Antigen
-
Cell Cycle
-
Cell Division
-
Gene Deletion
-
Immunoconjugates*
-
Lymphocyte Depletion
-
Lymphoid Tissue
-
Lymphoproliferative Disorders / immunology*
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Phenotype
Substances
-
Antigens, CD
-
Antigens, Differentiation
-
B7-1 Antigen
-
CD28 Antigens
-
CTLA-4 Antigen
-
Ctla4 protein, mouse
-
Immunoconjugates
-
Abatacept