Interleukin 12 exerts a differential effect on the maturation of neonatal and adult human CD45R0- CD4 T cells.

Shu, Uno; Demeure, Christian E.; Byun, Dae Gyoo; Podlaski, Frank J.; Stern, Alvin S.; Delespesse, Guy

doi:10.1172/jci117469

Cited by 44 publications

(22 citation statements)

References 53 publications

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“…The observation that IL-2, IL-4 and IL-7, but not IL-12, can reverse T cell 'anergy' provides a basis for the differential induction of PBMC from HIV-infected, non-vaccinated individuals by IL-7 and IL-12 [29]. In contrast, IL-12 seemed better than IL-7 at generating proliferative responses in naive, seronegative individuals, consistent with data suggesting that the priming of CD45RA þ , naive human CD4 þ cells with IL-12 and mitogen induces the generation of Th1-like CD45RO þ cells [32]. Several groups have recently proposed that HIV-1 pathogenesis is associated with a shift from beneficial Th1-like ('type 1') [33] cellular immune responses to detrimental Th2-like ('type 2') humoral responses [20,33,34].…”

Section: Differential Reversal Of Restricted Cellular Immunity Tosupporting

confidence: 75%

Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1

Kim

Loveland

Sitz

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe failure of immune effector mechanisms to control HIV-1 infection has important consequences for the human host. In a randomized cohort of HIV-infected patients, there was striking in vitro restriction of the proliferative response to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env. Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed the restriction in vitro, with Env recognition rising to 81%. Peripheral blood mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL-12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented proliferative responses to TT and gp160, whereas IL-12 only affected proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected placebo recipients who recognized rgp160. IL-12 had its greatest effect in the induction of rgp160-specific responses from seronegative individuals. The data suggest that these two cytokines have differential activity in the relief of restricted cellular immunity to Env; the predominant effect of IL-7 is in individuals who have been primed by exposure to antigen, while the effect of IL-12 is most evident in seronegative, unprimed individuals. Modification of restricted proliferative responses to Env by vaccination or cytokines in vitro suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively boost cellular reactivity to HIV-1.

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Section: Differential Reversal Of Restricted Cellular Immunity Tosupporting

confidence: 75%

Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1

Kim

Loveland

Sitz

et al. 1997

Clinical and Experimental Immunology

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“…In the Salmonella-harboring IL-12 plasmid vaccine model, IL-12 is involved in the protective response induced by administration and the level of protection is increased with co-administration of rIL-12 (Dunussi-Joannopoulos et al, 1999). IL-12 is involved in differentiation of naïve CD4+ lymphocyte to the Th1 subset, which produces IFN-γ, as well as other cytokines (Arulanandam et al, 1999;Shu et al, 1994). Many previous studies had tested this cytokine as an adjuvant in experimental infection models in which induction of Th1 responses is known to be critical for protective immunity (Arulanandam et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Salmonella typhimurium harboring plasmid expressing interleukin-12 induced attenuation of infection and protective immune responses

Yoon

Choi

Park

2011

J. Gen. Appl. Microbiol.

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“…In addition, IL-12 priming at birth may have a differential effect on the development of neonatal vs adult T cells. In vitro treatment of human neonatal T cells with IL-12 has been shown to induce both IFN-␥ and IL-4 secretion, a phenotype associated with maturation of neonatal T cells (35).…”

Section: Figurementioning

confidence: 99%

Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines

Arulanandam

Mittler

Lee

et al. 2000

The Journal of Immunology

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Neonates are highly susceptible to infectious agents and are known to display polarized expression of Th2-like cytokines and Abs. This neonatal immune bias has important implications for the development of vaccine strategies, particularly against viral infections. We now report that coadministration of IL-12 and an influenza subunit vaccine at birth enhances the protective efficacy of antiviral vaccination. Immunization and treatment with IL-12 within 24 h of birth resulted in elevated expression of IFN-γ, IL-10, and IL-15 mRNA in the spleens of newborn mice compared with animals exposed to vaccine only. In addition, these animals showed dramatic increases in IFN-γ-, IL-2-, and IL-4-secreting cells, and in IgG2a Ab levels upon adult challenge compared with mice primed with vaccine alone. Most importantly, animals vaccinated and simultaneously treated with IL-12 at birth displayed enhanced survival after lethal challenge with infectious influenza virus as adults compared with infected animals that had been primed with vaccine alone. This augmented protection required B cells and could be transferred to naive mice by immune serum. Collectively, these results provide evidence that administration of IL-12 to neonates induces a Th1-like response in newborns and elicits protective antiviral immune memory.

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Interleukin 12 exerts a differential effect on the maturation of neonatal and adult human CD45R0- CD4 T cells.

Cited by 44 publications

References 53 publications

Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1

Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1

Salmonella typhimurium harboring plasmid expressing interleukin-12 induced attenuation of infection and protective immune responses

Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines

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