Logo image
T cells undergo rapid ON/OFF but not ON/OFF/ON cycling of cytokine production in response to antigen
Journal article   Peer reviewed

T cells undergo rapid ON/OFF but not ON/OFF/ON cycling of cytokine production in response to antigen

Gail A Corbin and John T Harty
The Journal of immunology (1950), Vol.174(2), pp.718-726
01/15/2005
DOI: 10.4049/jimmunol.174.2.718
PMID: 15634891

View Online

Abstract

Inflammatory cytokines such as IFN-gamma and TNF produced by Ag-stimulated CD4(+) and CD8(+) T cells are important in defense against microbial infection. However, production of these cytokines must be tightly regulated to prevent immunopathology. Previous studies, conducted with BALB/c mice, have suggested that 1) CD8(+) T cells maintain IFN-gamma production but transiently produce TNF in the continued presence of Ag and 2) lymphocytic choriomeningitis virus-specific and in vitro-propagated effector CD8(+) T cells could rapidly cycle IFN-gamma production ON/OFF/ON in response to Ag exposure, removal, and re-exposure. In contrast with CD8(+) T cells, our results show that Listeria monocytogenes-specific CD4(+) T cells from C57BL/6 mice rapidly initiate (ON cycling) and maintain production of both IFN-gamma and TNF in the continued presence of Ag. Upon Ag removal, production of both cytokines rapidly ceases (OFF cycling). However, if the initial stimulation was maximal, Ag-specific CD4(+) T cells were unable to reinitiate cytokine production after a second Ag exposure. Furthermore, L. monocytogenes-specific CD8(+) T cells in the same mice and lymphocytic choriomeningitis virus-specific CD8(+) T cells in BALB/c mice also underwent ON/OFF cycling, but if the initial Ag stimulus was maximal, they could not produce IFN-gamma after Ag re-exposure. As the initial Ag dose was reduced, the number of cells producing cytokine in response to the second Ag exposure exhibited a corresponding increase. However, T cells that were marked for IFN-gamma secretion during the first stimulation did not contribute cytokine production during the second stimulation. Thus, T cells are not able to undergo rapid ON/OFF/ON cytokine cycling in vitro in response to Ag.
Lymphocytic choriomeningitis virus - immunology Tumor Necrosis Factor-alpha - metabolism T-Lymphocytes, Regulatory - metabolism Antigen-Presenting Cells - cytology Ovalbumin - immunology Cell Count Interferon-gamma - metabolism Listeria monocytogenes - immunology T-Lymphocytes, Regulatory - immunology CD4-Positive T-Lymphocytes - immunology Lymphocyte Activation - genetics Immunization, Secondary T-Lymphocytes - metabolism Peptide Fragments - immunology Listeriosis - immunology Mice, Inbred DBA Epitopes, T-Lymphocyte - immunology Nucleoproteins - immunology Ovalbumin - genetics Listeriosis - genetics Mice, Inbred C57BL CD4-Positive T-Lymphocytes - metabolism Cells, Cultured Ovalbumin - pharmacology Antigen-Presenting Cells - immunology Receptors, Antigen, T-Cell - physiology Animals T-Lymphocytes - cytology Cell Line, Tumor Listeria monocytogenes - genetics Immunologic Memory T-Lymphocytes - immunology Mice Mice, Inbred BALB C Antigens - pharmacology Tumor Necrosis Factor-alpha - biosynthesis Interferon-gamma - biosynthesis Antigens - genetics T-Lymphocytes, Regulatory - virology

Details

Metrics

Logo image