The rapidity with which virus-specific CD8+ T cells initiate IFN-gamma synthesis increases markedly over the course of infection and correlates with immunodominance.
Primary CD8+ T cell responses play a major role in controlling infection by many viruses, and CD8+ memory T cells can confer immunity to virus challenge. In this study we report that for many epitope-specific CD8+ T cell populations, the regulation of an important effector molecule, IFN-gamma, changes dramatically over the course of infection. During the acute phase of infection, many CD8+ T cells exhibit a significant lag before producing IFN-gamma in response to Ag contact; in contrast, the onset of IFN-gamma production by memory cells of the same epitope specificity is markedly accelerated. The biological consequences of this improved responsiveness are manifold. Moreover, during the acute phase of the CD8+ T cell response when immunodominance is being established, there is a strong correlation (p = 0.0002) between the abundance of each epitope-specific T cell population and the rapidity with which it initiates IFN-gamma synthesis. Previous studies have indicated that IFN-gamma plays a critical role in determining the immunodominance hierarchy of an on-going T cell response, and in this report we present evidence for an underlying mechanism: we propose that the CD8+ T cells that most rapidly initiate IFN-gamma production may be at a selective advantage, permitting them to dominate the developing T cell response.
Liu
Fei
F
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Whitton
J Lindsay
JL
Slifka
Mark K
MK
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D014777:Virus Diseases / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma