Naive CD8+ T Cells Do Not Require Costimulation for Proliferation and Differentiation into Cytotoxic Effector Cells

• Published in: The Journal of immunology (1950) 2000-02, Vol.164 (3), p.1216-1222
• Main Authors: Wang, Bo, Maile, Robert, Greenwood, Roberta, Collins, Edward J, Frelinger, Jeffrey A
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antigens, Viral; CD8 Antigens - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Separation; Glycoproteins - immunology; H-Y Antigen - immunology; Histocompatibility Antigens Class I - metabolism; Immunophenotyping; Interphase - genetics; Interphase - immunology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytic choriomeningitis virus - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - physiology; Signal Transduction - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Viral Proteins
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.3.1216

Most current models of T cell activation postulate a requirement for two distinct signals. One signal is delivered through the TCR by engagement with peptide/MHC complexes, and the second is delivered by interaction between costimulatory molecules such as CD28 and its ligands CD80 and CD86. Soluble peptide/MHC tetramers provide an opportunity to test whether naive CD8+ T cells can be activated via the signal generated through the TCR-alphabeta in the absence of any potential costimulatory molecules. Using T cells from two different TCR transgenic mice in vitro, we find that TCR engagement by peptide/MHC tetramers is sufficient for the activation of naive CD8+ T cells. Furthermore, these T cells proliferate, produce cytokines, and differentiate into cytolytic effectors. Under the conditions where anti-CD28 is able to enhance proliferation of normal B6 CD4+, CD8+, and TCR transgenic CD8+ T cells with anti-CD3, we see no effect of anti-CD28 on proliferation induced by tetramers. The results of this experiment argue that given a strong signal delivered through the TCR by an authentic ligand, no costimulation is required.