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CTLA-4 is a T cell surface receptor essential for the negative regulation of T cell activation. In the CTLA-4-deficient mouse, a dramatic accumulation of activated peripheral T cells effects extensive damage to host tissues, resulting in mortality within 5 weeks of age. To determine whether the accumulation of activated T cells in CTLA-4(-/-) mice is due to a defect in thymic selection, we examined negative selection in CTLA-4(-/-) mice using two transgenic T cell receptor (TCR) models of thymic selection. Neither the H-Y-specific TCR nor the lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic models revealed a defect in positive or negative selection in CTLA-4(-/-) mice in vivo or in vitro. In fact, the negatively selecting phenotype of male H-YTCR-transgenic mice greatly mitigated the accumulation of activated peripheral T cells. Further, peripheral CTLA-4(-/-) T cells expressing a single LMCV-specific transgenic TCR did not have an activated phenotype, indicating that CTLA-4(-/-) T cells require specific antigen for proliferation. These results demonstrate that specific antigen is required for the lymphoproliferation observed in CTLA-4(-/-) mice, and that CTLA-4 deficiency does not lead to a gross defect in negative selection.

Original publication




Journal article


Eur J Immunol

Publication Date





1887 - 1892


Abatacept, Animals, Antigens, CD, Antigens, Differentiation, Apoptosis, Base Sequence, CTLA-4 Antigen, Cell Survival, DNA Primers, Female, H-Y Antigen, Immunoconjugates, Lymphocyte Activation, Lymphocytic choriomeningitis virus, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Thymus Gland