Limits...
Absence of both IL-7 and IL-15 severely impairs the development of CD8 T cell response against Toxoplasma gondii.

Bhadra R, Guan H, Khan IA - PLoS ONE (2010)

Bottom Line: However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8(+) T cells.Interestingly, the absence of both cytokines did not impair initial CD8(+) T cell generation but affected their survival and differentiation into memory phenotype IL-7Ralpha(hi) cells.To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8(+) T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC., USA.

ABSTRACT
CD8(+) T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8(+) T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related gamma-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8(+) T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8(+) T cell response. This impairment is characterized by reduction in CD44 expression, IFN-gamma production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8(+) T cells. Interestingly, the absence of both cytokines did not impair initial CD8(+) T cell generation but affected their survival and differentiation into memory phenotype IL-7Ralpha(hi) cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8(+) T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15(-/-) mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8(+) T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8(+) T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported.

Show MeSH

Related in: MedlinePlus

Cps vaccination elicits a sub-optimal CD8+ T cells response in IL-7 depleted KO mice.Splenocytes were harvested from KO and anti IL-7 treated KO mice infected with 1×106 parasites of cps1-1 at day 14 p.i. A, Absolute number of CD8+CD44int/hi T cells present in untreated or antibody treated infected or naïve KO mice is shown in the top panel. B, For evaluation of cytokine response splenocytes were stimulated in anti CD3 coated plates and then stained for CD8β, CD44 and IFN-γ as described in Materials and Methods. The experiment was repeated twice with similar results and the data depicted is representative of one of two experiments with 3–4 mice per group.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2877110&req=5

pone-0010842-g007: Cps vaccination elicits a sub-optimal CD8+ T cells response in IL-7 depleted KO mice.Splenocytes were harvested from KO and anti IL-7 treated KO mice infected with 1×106 parasites of cps1-1 at day 14 p.i. A, Absolute number of CD8+CD44int/hi T cells present in untreated or antibody treated infected or naïve KO mice is shown in the top panel. B, For evaluation of cytokine response splenocytes were stimulated in anti CD3 coated plates and then stained for CD8β, CD44 and IFN-γ as described in Materials and Methods. The experiment was repeated twice with similar results and the data depicted is representative of one of two experiments with 3–4 mice per group.

Mentions: Animal studies were carried out in agreement with Institutional Animal Care and Use Committee approved guidelines at George Washington University Medical Center. 6 to 8 week old female IL-15−/− mice (Taconic Farms) and C57BL/6 mice (NCI) were infected per-orally with 10 cysts of ME49 strain (Figure. 1–6) of T. gondii. CD8+ T cell responses were evaluated at day 14 post-infection (p.i.). Anti IL-7 antibody (M25) was a kind gift from Amgen. The antibody was injected into wild-type or IL-15−/− i.p. (intraperitoneally) at 0.5 mg per mouse at 3-day intervals. The treatment was initiated one day before infection and continued till termination of experiment. Control mice were injected with equal volume of saline. For some experiments, IL-15−/− and anti IL-7 treated IL-15−/− animals were infected i.p. with 1×106 cps1-1 parasites (Figure. 7) and CD8+ T cell responses were evaluated at day 14 p.i..


Absence of both IL-7 and IL-15 severely impairs the development of CD8 T cell response against Toxoplasma gondii.

Bhadra R, Guan H, Khan IA - PLoS ONE (2010)

Cps vaccination elicits a sub-optimal CD8+ T cells response in IL-7 depleted KO mice.Splenocytes were harvested from KO and anti IL-7 treated KO mice infected with 1×106 parasites of cps1-1 at day 14 p.i. A, Absolute number of CD8+CD44int/hi T cells present in untreated or antibody treated infected or naïve KO mice is shown in the top panel. B, For evaluation of cytokine response splenocytes were stimulated in anti CD3 coated plates and then stained for CD8β, CD44 and IFN-γ as described in Materials and Methods. The experiment was repeated twice with similar results and the data depicted is representative of one of two experiments with 3–4 mice per group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2877110&req=5

pone-0010842-g007: Cps vaccination elicits a sub-optimal CD8+ T cells response in IL-7 depleted KO mice.Splenocytes were harvested from KO and anti IL-7 treated KO mice infected with 1×106 parasites of cps1-1 at day 14 p.i. A, Absolute number of CD8+CD44int/hi T cells present in untreated or antibody treated infected or naïve KO mice is shown in the top panel. B, For evaluation of cytokine response splenocytes were stimulated in anti CD3 coated plates and then stained for CD8β, CD44 and IFN-γ as described in Materials and Methods. The experiment was repeated twice with similar results and the data depicted is representative of one of two experiments with 3–4 mice per group.
Mentions: Animal studies were carried out in agreement with Institutional Animal Care and Use Committee approved guidelines at George Washington University Medical Center. 6 to 8 week old female IL-15−/− mice (Taconic Farms) and C57BL/6 mice (NCI) were infected per-orally with 10 cysts of ME49 strain (Figure. 1–6) of T. gondii. CD8+ T cell responses were evaluated at day 14 post-infection (p.i.). Anti IL-7 antibody (M25) was a kind gift from Amgen. The antibody was injected into wild-type or IL-15−/− i.p. (intraperitoneally) at 0.5 mg per mouse at 3-day intervals. The treatment was initiated one day before infection and continued till termination of experiment. Control mice were injected with equal volume of saline. For some experiments, IL-15−/− and anti IL-7 treated IL-15−/− animals were infected i.p. with 1×106 cps1-1 parasites (Figure. 7) and CD8+ T cell responses were evaluated at day 14 p.i..

Bottom Line: However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8(+) T cells.Interestingly, the absence of both cytokines did not impair initial CD8(+) T cell generation but affected their survival and differentiation into memory phenotype IL-7Ralpha(hi) cells.To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8(+) T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC., USA.

ABSTRACT
CD8(+) T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8(+) T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related gamma-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8(+) T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8(+) T cell response. This impairment is characterized by reduction in CD44 expression, IFN-gamma production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8(+) T cells. Interestingly, the absence of both cytokines did not impair initial CD8(+) T cell generation but affected their survival and differentiation into memory phenotype IL-7Ralpha(hi) cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8(+) T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15(-/-) mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8(+) T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8(+) T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported.

Show MeSH
Related in: MedlinePlus