Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells

Immunity. 1997 Dec;7(6):885-95. doi: 10.1016/s1074-7613(00)80406-9.


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


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Abatacept