IFN-gamma and IL-4 regulate the growth and differentiation of CD8+ T cells into subpopulations with distinct cytokine profiles.
In this study, we have investigated the effects of IL-4 and IFN-gamma on the growth and differentiation of CD8+ T cells in vitro. Rat splenic CD8+ T cells expressed higher levels of IL-4, IL-5, IL-10, and IFN-gamma mRNA, as measured by reverse-transcription PCR, than CD4+ T cells from the same source, whereas CD4+ T cells expressed more IL-2 and IL-6 mRNA. CD8+ T cells were cultured for 6 days with PMA, ionomycin, and IL-2, and their ability to proliferate, to express mRNA for IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma, and to secrete IFN-gamma and IL-2 was determined. IL-4 could act as a growth factor for CD8+ T cells during primary stimulation, but inhibited proliferation of the restimulated 6-day-cultured CD8+ T cells. The highest levels of mRNA for IL-2 and IL-6 were detected in control cultures in which little mRNA for IL-4, IL-5, or IL-10 was detected. Addition of IL-4 to the primary cultures reduced the capacity of the restimulated cells to express mRNA for IL-2, and for IL-6, but enhanced expression of mRNA for IL-4 and IL-5. Addition of IFN-gamma to the cultures, alone or in conjunction with IL-4, or addition of IFN-gamma-specific neutralizing Ab, had little effect. However, in conjunction with IL-4, anti-IFN-gamma enhanced expression of mRNA for IFN-gamma, and for IL-10. These results indicate that IL-4 and IFN-gamma regulate the differentiation of CD8+ T cells and the growth of cytotoxic and other types of CD8+ T cells, and suggest pathways through which CD8+ T cells may interact with other immune cells.
Noble
A
A
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London, UK.
Macary
P A
PA
Kemeny
D M
DM
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000187:drug effects*
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma