Medical College of Wisconsin
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CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production. J Immunol 1992 Dec 15;149(12):3795-801



Pubmed ID


Scopus ID

2-s2.0-0027057908   148 Citations


Ag-presenting cells provide at least two distinct signals for T cell activation. T cell receptor-dependent stimulation is provided by presentation of a specific peptide Ag in association with MHC molecules. In addition, APC also supply costimulatory signals required for T cell activation that are neither Ag- nor MHC restricted. One such costimulatory signal is mediated via the interaction of B7 on APC with the CD28 receptor on T cells. Recently, CTLA-4 has been shown to be a second B7 receptor on T cells. In the present report, we have examined the expression of CD28 and CTLA-4 on a panel of resting and activated normal T cell subsets and T cell clones by RNA blot analysis in an attempt to determine whether their expression defines reciprocal or overlapping subsets. CD28 was detected in resting T cells, whereas CTLA-4 was not. After stimulation with PHA and PMA for 24 h, CTLA-4 mRNA was expressed in both the CD4+ and CD8+ subsets as well as in CD28+ T cells. We examined 37 human and six murine T cell clones that had been previously characterized for their cytokine production. After activation, CTLA-4 and CD28 mRNA were coexpressed in 36 of 37 human T cell clones and all six murine T cell clones. These included T cells of CD4+8-, CD4-8+, and CD4-8- phenotypes as well as clones with Th1 and Th2 cytokine profiles. In contrast, CD28 but not CTLA-4 mRNA was detected in leukemic T cell lines and myelomas. CTLA-4 and B7 mRNA but not CD28 mRNA was detected in two long term HTLV-I-transformed T cell lines. These data demonstrate that CD28 and CTLA-4 mRNA are coexpressed in most activated T cells and T cell clones, providing evidence that they do not define reciprocal subsets. Moreover, they are consistent with the hypothesis that B7 transmits its signal through a single receptor, CD28, on resting T cells, and multiple receptors, CD28 and CTLA-4, on activated T cells.

Author List

Freeman GJ, Lombard DB, Gimmi CD, Brod SA, Lee K, Laning JC, Hafler DA, Dorf ME, Gray GS, Reiser H


Staley A. Brod MD Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigens, CD
Antigens, Differentiation
Antigens, Differentiation, T-Lymphocyte
Antigens, Surface
B7-1 Antigen
Base Sequence
Blotting, Northern
CD28 Antigens
CTLA-4 Antigen
Cell Adhesion Molecules
Cell Line
Leukemia, T-Cell
Lymphocyte Activation
Molecular Sequence Data
Oligonucleotide Probes
Polymerase Chain Reaction
RNA, Messenger
Tumor Necrosis Factor-alpha