A clonal culture system demonstrates that IL-4 induces a subpopulation of noncytolytic T cells with low CD8, perforin, and granzyme expression

Kienzle, Norbert, Buttigieg, Kathy, Groves, Penny, Kawula, Tom and Kelso, Anne (2002) A clonal culture system demonstrates that IL-4 induces a subpopulation of noncytolytic T cells with low CD8, perforin, and granzyme expression. Journal of Immunology, 168 4: 1672-1681.


Author Kienzle, Norbert
Buttigieg, Kathy
Groves, Penny
Kawula, Tom
Kelso, Anne
Title A clonal culture system demonstrates that IL-4 induces a subpopulation of noncytolytic T cells with low CD8, perforin, and granzyme expression
Journal name Journal of Immunology
Publication date 2002
Sub-type Article
Volume number 168
Issue number 4
ISSN 0022-1767; 1550-6606
Start page 1672
End page 1681
Total pages 10
Editor R. R. Rich
M. M. Hogan
Place of publication Bethesda, U.S.A.
Publisher American Association of Immunologists
Collection year 2002
Language eng
Subject C1
320202 Cellular Immunology
730102 Immune system and allergy
Abstract Immune deviation of cytolytic T cell function, induced by type 2 cytokines like IL-4, is an attractive concept to explain failure of the immune system in some diseases. However, this concept is challenged by previous conflicting results on whether type 2 cytokine-producing CD8(+) T cells are cytolytic. Therefore, we have analyzed the relationship between cytolytic activity and cytokine production among large numbers of primary CD8(+) T cell clones. Single murine CD8(+) T cells of naive phenotype were activated at high efficiency with immobilized Abs to CD3, CD8, and CD11a in the presence of IL-2 (neutral conditions) or IL-2, IL-4, and anti-IFN-gamma Ab (type 2-polarizing conditions) for 8-9 days. Under neutral conditions, most clones produced IFN-gamma without IL-4 and were cytolytic. Under type 2-polarizing conditions, most clones produced IFN-gamma and IL-4 but displayed variable cytolytic activity and CD8 expression. Separation on the basis of surface CD8 levels revealed that, compared with CD8(high) cells from the same cultures, CD8(low) cells were poorly cytolytic and expressed low levels of perforin mRNA and protein and granzyme A, B, and C mRNA. A similar, smaller population of noncytolytic CD8(low) cells was identified among CD8(low) T cells activated in mixed lymphocyte reaction with IL-4. Variable efficiency of generation of the noncytolytic cells may account for the differing results of earlier studies. We conclude that IL-4 promotes the development of a noncytolytic CD8(low) T cell phenotype that might be important in tumor- or pathogen-induced immune deviation.
Keyword Immunology
Granule-mediated Apoptosis
Stimulatory Factor
Protein Immunization
Ifn-gamma
In-vivo
Effector Populations
Cytokine Profiles
Virus-infection
Lymphocytes-t
Interleukin-4
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collection: School of Medicine Publications
 
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