CD28 co-stimulation results in down-regulation of lymphotactin expression in human CD4(+) but not CD8(+) T cells via an IL-2-dependent mechanism.
Chemokines are key molecules in promoting leukocyte migration and, for some of them, T cell adhesion and activation. Lymphotactin, which is the unique known member of the C class of chemokines, is produced by and acts on T lymphocytes, but the requirement of co-stimulatory pathways such as CD28 for its expression is largely unknown. CD28 plays a dominant role in the amplification of T cell proliferation, survival and cytokine production. In this report, we demonstrate that human lymphotactin expression, at both the mRNA and protein levels, is optimally induced by CD3/TCR activation alone, whereas CD28 co-stimulation turns off this expression. This down-regulation is not attributable to secondary activation via CTLA-4, the alternative counter-receptor of B7 ligands. Only the CD4(+) and not the CD8(+) subset is directly affected by this negative regulation. Transcript destabilization can be ruled out as a mechanism by which CD28 down-regulates lymphotactin expression. However, such down-regulation can be partly induced by IL-2 and abrogated by blocking IL-2/IL-2 receptor interaction. This particular profile of lymphotactin expression is not in line with the prevailing dogma of up-regulation of cytokine gene expression by CD28 co-stimulation, and represents a new CD28-mediated regulatory mechanism for lymphotactin expression.
Olive
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Unit 119 of the National Institute of Health and Medical Research, Marseille, France.
Cerdan
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D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D019744:Chemokines, C; D015536:Down-Regulation; D006801:Humans; D018796:Immunoconjugates; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019744:Chemokines, C; D018796:Immunoconjugates; D007376:Interleukin-2; D008222:Lymphokines; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C018997:lymphotactin; D000069594:Abatacept