Teaching tired T cells to fight HIV: time to test IL-15 for immunotherapy?

Mastroianni, Claudio Maria; d’Ettorre, Gabriella; Forcina, Gabriele; Vullo, Vincenzo

doi:10.1016/j.it.2004.01.002

Cited by 38 publications

(21 citation statements)

References 48 publications

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“…IL-15 is currently proposed as adjuvant immunotherapy for HIV ϩ individuals (18,53,54) and has also been shown to curtail infections by human herpesviruses (33). Our data indicate that it may also be beneficial in HCV infection, where IFN-␣ treatment is already used, and may potentially be useful in other chronic infections too.…”

Section: Cd28mentioning

confidence: 69%

Shared Alterations in NK Cell Frequency, Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections

Meier

Owen

Taylor

et al. 2005

J Virol

165

145

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Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause clinically important persistentinfections. The effects of virus persistence on innate immunity, including NK cell responses, and the underlying mechanisms are not fully understood. We examined the frequency, phenotype, and function of peripheral blood CD3 ؊ CD56 ؉ NK subsets in HIV ؉ and HCV ؉ patients and identified significantly reduced numbers of total NK cells and a striking shift in NK subsets, with a marked decrease in the CD56 dim cell fraction compared to CD56 bright cells, in both infections. This shift influenced the phenotype and functional capacity (gamma interferon production, killing) of the total NK pool. In addition, abnormalities in the functional capacity of the CD56 dim NK subset were observed in HIV ؉ patients. The shared NK alterations were found to be associated with a significant reduction in serum levels of the innate cytokine interleukin 15 (IL-15). In vitro stimulation with IL-15 rescued NK cells of HIV ؉ and HCV ؉ patients from apoptosis and enhanced proliferation and functional activity. We hypothesize that the reduced levels of IL-15 present in the serum during HIV and HCV infections might impact NK cell homeostasis, contributing to the common alterations of the NK pool observed in these unrelated infections.

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Section: Cd28mentioning

confidence: 69%

Shared Alterations in NK Cell Frequency, Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections

Meier

Owen

Taylor

et al. 2005

J Virol

165

145

View full text Add to dashboard Cite

show abstract

“…Because of IL-15's exquisite specificity -in terms of both its selective targeting of T EM and transitional memory T cell populations and its focus on proliferation rather than other aspects of activation -we would posit that IL-15 therapy would enhance CD4 + T EM cell reconstitution without the deleterious effects of generalized immune activation. Moreover, the ability of IL-15 to promote CD8 + T EM cell expansion, survival, and function (18,24,25,45) would likely enhance immunity against HIV and opportunistic pathogens, providing further benefit. Indeed, we demonstrate IL-15-mediated induction of proliferation for both SIV-and CMV-specific CD8 + T cells here ( Figure 9C).…”

Section: Figurementioning

confidence: 99%

IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates

Picker¹

2006

Journal of Clinical Investigation

182

254

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“…Thus, IL-15 promotes extrathymic development of T and NK cells (22), is a growth, differentiation, activation, and survival factor for NK cells that contributes to increased cytolytic activity of NK cells, stimulation of cytokine (IFN-␥) synthesis, and prolongation of NK cell survival (23,24). IL-15 is also a potent T cell growth factor that enhances the survival, activation, IFN-␥ production, and cytotoxicity of CD8 ϩ T cells and has an important role in regulating CD8 ϩ T cell homeostasis (25). IL-15 regulates both proliferation and Ab production by activated B cells (26), while mast cells proliferate in response to IL-15 and produce functionally active IL-4 (27).…”

Section: Molecular and Functional Characterization Of Il-15 In Rainbomentioning

confidence: 99%

Molecular and Functional Characterization of IL-15 in Rainbow TroutOncorhynchus mykiss:A Potent Inducer of IFN-γ Expression in Spleen Leukocytes

Wang

Holland

Carrington

et al. 2007

The Journal of Immunology

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IL-15 is a member of the common γ-chain family of cytokines that possess a heterogeneous repertoire of activities on various cells of the immune system. We report here the first functional characterization of a fish IL-15 in rainbow trout. The trout IL-15 gene is 6-kb long and contains six exons and five introns that transcribe into a 1.2-kb mRNA containing seven out-of-frame AUG initiation codons and translate into a 193-aa peptide. Potential sites for transcriptional activators and repressors have been identified in the trout IL-15 gene. Like IL-15 from other species, trout IL-15 is closely linked to an INPP4B gene, but there is also a BCL10 gene located between the IL-15 and INPP4B genes. Three alternative splicing variants of the trout IL-15 gene have also been identified and their expression in vivo was studied. Trout IL-15 expression is present in all the tissues and cell lines studied. Recombinant trout IFN-γ selectively increased IL-15 expression but had little effect on other cytokines such as IL-1β and IL-11. Recombinant trout IL-15 preferentially stimulated splenic leukocytes from healthy fish, where it induced a large increase in IFN-γ expression, with little, if any, effect on IL-1β expression. This effect was quite long-lived, and was still apparent 24 h poststimulation. Although the exact cell types being affected have still to be determined, it is clear that once produced IL-15 will have a profound affect on the ability of the fish immune system to activate antimicrobial defenses and genes induced themselves by IFN-γ.

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Teaching tired T cells to fight HIV: time to test IL-15 for immunotherapy?

Cited by 38 publications

References 48 publications

Shared Alterations in NK Cell Frequency, Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections

Shared Alterations in NK Cell Frequency, Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections

IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates

Molecular and Functional Characterization of IL-15 in Rainbow TroutOncorhynchus mykiss:A Potent Inducer of IFN-γ Expression in Spleen Leukocytes

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