Exaggerated proinflammatory and Th1 responses in the absence of gamma/delta T cells after infection with Listeria monocytogenes.
While gamma/delta T cells are involved in host defense and immunopathology in a variety of infectious diseases, their precise role is not yet clearly defined. In the absence of gamma/delta T cells, mice die after infection with a dose of Listeria monocytogenes that is not lethal in immunologically intact animals. Morbidity might result from insufficient levels of cytokines normally produced by gamma/delta T cells or conversely from an excess of cytokines due to a lack of down-regulation of the inflammatory response in the absence of gamma/delta T cells. Consistent with a regulatory role, we found that systemic levels of proinflammatory cytokines (interleukin-6 [IL-6], IL-12, and gamma interferon [IFN-gamma]) were significantly higher in the absence of gamma/delta T cells during the innate phase of the response. Using combinations of genetically altered and immunodepleted mice, we found evidence for gamma/delta T-cell-mediated regulation of IFN-gamma production by multiple cell types of both lymphoid and myeloid lineages. The antigen-specific alpha/beta T-cell response that followed the exaggerated innate response was also increased in gamma/delta T-cell-deficient mice. These findings are consistent with an emerging picture from a variety of immune response models of a critical role for gamma/delta T cells in down-modulation of the immune response.
Skeen
M J
MJ
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Rix
E P
EP
Freeman
M M
MM
Ziegler
H K
HK
D000220:Adaptation, Biological; D000818:Animals; D001202:Ascitic Fluid; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008088:Listeriosis / Q000276:immunology* / Q000401:mortality; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D015850:Interleukin-6; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12; D007371:Interferon-gamma