Functional Heterogeneity of Cytokines and Cytolytic Effector Molecules in Human CD8+ T Lymphocytes

• Published in: The Journal of immunology (1950) Vol. 167; no. 1; pp. 181 - 187
• Main Authors: Sandberg, Johan K, Fast, Noam M, Nixon, Douglas F
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-07-2001
• Subjects: Antigens, Surface - biosynthesis; Biomarkers; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - enzymology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation - immunology; Cell Line; Cytokines - biosynthesis; Cytokines - physiology; Cytotoxicity, Immunologic - physiology; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Granzymes; Humans; Immunophenotyping; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - physiology; Perforin; Phosphoproteins - immunology; Phosphoproteins - metabolism; Pore Forming Cytotoxic Proteins; Serine Endopeptidases - biosynthesis; Serine Endopeptidases - physiology; T-Lymphocyte Subsets - enzymology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - virology; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - enzymology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - virology; Tumor Necrosis Factor-alpha - biosynthesis; Viral Matrix Proteins - immunology; Viral Matrix Proteins - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.1.181

CD8(+) T cells use a number of effector mechanisms to protect the host against infection. We have studied human CD8(+) T cells specific for CMV pp65(495-503) epitope, or for staphylococcal enterotoxin B, for the expression patterns of five cytokines and cytolytic effector molecules before and after antigenic stimulation. Ex vivo, the cytolytic molecule granzyme B was detected in a majority of circulating CMV-specific CD8(+) T cells, whereas perforin was rarely expressed. Both were highly expressed after Ag-specific activation accompanied by CD45RO up-regulation. TNF-alpha, IFN gamma, and IL-2 were sequentially acquired on recognition of Ag, but surprisingly, only around half of the CMV-specific CD8(+) T cells responded to antigenic stimuli with production of any cytokine measured. A dominant population coexpressed TNF-alpha and IFN-gamma, and cells expressing TNF-alpha only, IFN-gamma only, or all three cytokines together also occurred at lower but clearly detectable frequencies. Interestingly, perforin expression and production of IFN-gamma and TNF-alpha in CD8(+) T cells responding to staphylococcal enterotoxin B appeared to be largely segregated, and no IL-2 was detected in perforin-positive cells. Together, these data indicate that human CD8(+) T cells can be functionally segregated in vivo and have implications for the understanding of human CD8(+) T cell differentiation and specialization and regulation of effector mechanisms.