IL-15 preferentially enhances functional properties and antigen-specific responses of CD4+CD28(null) compared to CD4+CD28+ T cells.

Abstract

One of the most prominent changes during T-cell aging in humans is the accumulation of CD28(null) T cells, mainly CD8+ and also CD4+ T cells. Enhancing the functional properties of these cells may be important as they provide an antigen-specific defense against chronic infections. Recent studies have shown that IL-15 does in fact play an appreciable role in CD4 memory T cells under physiological conditions. We found that treatment with IL-15 increased the frequency of elderly CD4+CD28(null) T cells by the preferential proliferation of these cells compared to CD4+CD28+ T cells. IL-15 induced an activated phenotype in CD4+CD28(null) T cells. Although the surface expression of IL-15R α-chain was not increased, the transcription factor STAT-5 was preferentially activated. IL-15 augmented the cytotoxic properties of CD4+CD28(null) T cells by increasing both the mRNA transcription and storage of granzyme B and perforin for the cytolytic effector functions. Moreover, pretreatment of CD4+CD28(null) T cells with IL-15 displayed a synergistic effect on the IFN-γ production in CMV-specific responses, which was not observed in CD4+CD28+ T cells. IL-15 could play a role enhancing the effector response of CD4+CD28(null) T cells against their specific chronic antigens.

• Authors: Rebeca Alonso-Arias, Marco A Moro-García, José R Vidal-Castiñeira, Juan J Solano-Jaurrieta, Francisco M Suárez-García, Eliecer Coto, Carlos López-Larrea
• Journal: Aging cell (Aging Cell) Vol. 10 Issue 5 Pg. 844-52 (Oct 2011) ISSN: 1474-9726 [Electronic] England
• PMID: 21635686 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Chemical References

• Antibodies, Viral
• Biomarkers
• CD28 Antigens
• Interleukin-15
• RNA, Messenger
• Recombinant Proteins
• STAT5 Transcription Factor
• Perforin
• Interferon-gamma
• Granzymes

Topics

• Aged
• Aged, 80 and over
• Antibodies, Viral (analysis)
• Biomarkers
• CD28 Antigens (analysis, immunology)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cell Proliferation
• Cytomegalovirus (immunology)
• Granzymes (metabolism)
• Humans
• Interferon-gamma (immunology, metabolism)
• Interleukin-15 (immunology, pharmacology)
• Leukocytes, Mononuclear (drug effects, immunology)
• Lymphocyte Activation
• Perforin (metabolism)
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (immunology, pharmacology)
• STAT5 Transcription Factor (genetics, metabolism)