Interleukin-4 and interferon-gamma regulate differentiation of CD8+ T cells into populations with divergent cytokine profiles.
The ability of CD8+ T cells to synthesise and secrete cytokines before and after culture with interleukin (IL)-4 and anti-interferon (IFN)-gamma was investigated. Purified rat splenic CD8+ and CD4+ T cells and CD4-CD8- cells were stimulated with phorbol myristate acetate (PMA) and ionomycin for 6 h and expression of mRNA for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN-gamma determined using a quantitative PCR technique. Secreted IFN-gamma and IL-2 were measured by ELISA and bioassay, respectively, 24 h after restimulation. The highest levels of IL-4, IL-5 and IFN-gamma mRNA were expressed by CD8+ T cells, the highest levels of message for IL-2 were expressed by CD4+ T cells and the highest levels of message for IL-6 and IL-10 by CD4-CD8- splenocytes. Purified rat splenic CD8+ T cells were cultured for 6 days with PMA, ionomycin and IL-2 with or without IL-4 or anti-IFN-gamma and restimulated with PMA and ionomycin. Those CD8+ T cells cultured with IL-4 expressed increased levels of IL-4, IL-5 and reduced levels of IL-2 and IL-6 mRNA, while CD8+ T cells cultured with IL-4 and anti-IFN-gamma expressed increased levels of mRNA for IL-10 and IFN-gamma. Comparable effects were seen for secreted IFN-gamma and IL-2. These results indicate that CD8+ T cells have the potential to produce large amounts of Th2 cytokines and are able to differentiate into different subpopulations with distinct cytokine profiles under the control of IL-4 and IFN-gamma.
Noble
A
A
Department of Allergy and Respiratory Medicine, Guy's and St Thomas's Hospital, London, UK.
Kemeny
D M
DM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013154:Spleen / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007378:Interleukins; D008222:Lymphokines; D012333:RNA, Messenger; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate