Lack of CD4+T Cells Does Not Affect Induction of CD8+T-Cell Immunity againstEncephalitozoon cuniculiInfection

Moretto, Magali; Casciotti, Lori; Durell, Brigit G.; Khan, Imtiaz Ali

doi:10.1128/iai.68.11.6223-6232.2000

Cited by 51 publications

(40 citation statements)

References 39 publications

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“…Coordinated interaction between CD4 ϩ and CD8 ϩ T cells was required to resolve an infection with the intracellular bacterium Listeria monocytogenes (44). However, the absence of CD4 ϩ T cells did not affect the CD8 ϩ -T-cell response against an Encephalitozoon cuniculi infection (31). Similar to these findings, our findings showed that a CD8…”

Section: The Role Of Conventional Cd4supporting

confidence: 81%

CD8⁺-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4⁺T Cells

Casciotti¹,

Ely²,

Williams

et al. 2002

Infect Immun

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T-cell immunity is critical for survival of hosts infected with Toxoplasma gondii. Among the cells in the T-cell population, CD8+ T cells are considered the major effector cells against this parasite. It is believed that CD4+ T cells may be crucial for induction of the CD8+-T-cell response against T. gondii. In the present study, CD4−/− mice were used to evaluate the role of conventional CD4+ T cells in the immune response against T. gondii infection. CD4−/− mice infected with T. gondii exhibited lower gamma interferon (IFN-γ) messages in the majority of their tissues. As a result, mortality due to a hyperinflammatory response was prevented in these animals. Interestingly, T. gondii infection induced a normal antigen-specific CD8+-T-cell immune response in CD4−/− mice. No difference in generation of precursor cytotoxic T lymphocytes (pCTL) or in IFN-γ production by the CD8+-T-cell populations from the knockout and wild-type animals was observed. However, the mutant mice were not able to sustain CD8+-T-cell immunity. At 180 days after infection, the CD8+-T-cell response in the knockout mice was depressed, as determined by pCTL and IFN-γ assays. Loss of CD8+-T-cell immunity at this time was confirmed by adoptive transfer experiments. Purified CD8+ T cells from CD4−/− donors that had been immunized 180 days earlier failed to protect the recipient mice against a lethal infection. Our study demonstrated that although CD8+-T-cell immunity can be induced in the absence of conventional CD4+ T cells, it cannot be maintained without such cells

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Section: The Role Of Conventional Cd4supporting

confidence: 81%

CD8⁺-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4⁺T Cells

Casciotti¹,

Ely²,

Williams

et al. 2002

Infect Immun

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“…Due to their early rise, this T cell subset is an important source of cytokines, which induce the CD8 ϩ T cell response against the parasite. A recent study from our laboratory reported that adequate CD8 ϩ T cell immune response against E. cuniculi infection can be launched in CD4 ϩ T cell-deficient mice (32). These findings raised an important question about the mechanism of CD8 ϩ T cell priming in the absence of conventional CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 84%

γδ T Cell-Deficient Mice Have a Down-Regulated CD8+ T Cell Immune Response AgainstEncephalitozoon cuniculiInfection

Moretto

Durell

Schwartzman³

et al. 2001

The Journal of Immunology

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γδ T cells have been reported to play an essential effector role during the early immune response against a wide variety of infectious agents. Recent studies have suggested that the γδ T cell subtype may also be important for the induction of adaptive immune response against certain microbial pathogens. In the present study, an early increase of γδ T cells during murine infection with Encephalitozoon cuniculi, an intracellular parasite, was observed. The role of γδ T cells against E. cuniculi infection was further evaluated by using gene-knockout mice. Mice lacking γδ T cells were susceptible to E. cuniculi infection at high challenge doses. The reduced resistance of δ−/− mice was attributed to a down-regulated CD8+ immune response. Compared with parental wild-type animals, suboptimal Ag-specific CD8+ T cell immunity against E. cuniculi infection was noted in δ−/− mice. The splenocytes from infected knockout mice exhibited a lower frequency of Ag-specific CD8+ T cells. Moreover, adoptive transfer of immune TCRαβ+ CD8+ T cells from the δ−/− mice failed to protect naive CD8−/− mice against a lethal E. cuniculi challenge. Our studies suggest that γδ T cells, due to their ability to produce cytokines, are important for the optimal priming of CD8+ T cell immunity against E. cuniculi infection. This is the first evidence of a parasitic infection in which down-regulation of CD8+ T cell immune response in the absence of γδ T cells has been demonstrated.

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“…The experiment was performed twice, and the results are representative of one experiment. The importance of CD8 ϩ T cells in protection against E. cuniculi infection has been well established by studies conducted by us and in other laboratories (1,2,16,20,21). CD8 ϩ T-cell-deficient animals are highly susceptible to this pathogen, and infected mice exhibit severe morbidity before death.…”

Section: Fig 8 Augmentation Of the Il-12-mediated Cd8mentioning

confidence: 93%

“…DNA was extracted from tissues by using a DNeasy blood and tissue kit (Qiagen, Valencia CA), and 400 ng of each sample was assayed by real-time PCR using the following primers specific for E. cuniculi: ECUNF (5Ј-ATG AGAAGTGATGTGTGCG-3Ј) and ECUNR (5Ј-TGCCATGCACTCACAG GCATC-3Ј) (20). Amplification was performed with a Bio-Rad iCycler (BioRad, Hercules, CA) using the following conditions: 40 cycles of 94°C for 45 s, 53°C for 1 min, and 72°C for 30s.…”

Section: Methodsmentioning

confidence: 99%

Lack of Interleukin-12 in p40-Deficient Mice Leads to Poor CD8⁺T-Cell Immunity againstEncephalitozoon cuniculiInfection

2010

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A CD8؉ T-cell response is critical for protection against Encephalitozoon cuniculi infection. However, the factors responsible for the generation of CD8 ؉ T-cell immunity during E. cuniculi infection and the cytokines involved in this process have not been identified. In the present study, we demonstrated that p40-deficient animals, which are unable to produce interleukin-12 (IL-12), have a serious defect in expansion of the CD8 ؉ T-cell response which compromises the survival of an infected host. Adoptive transfer of CD8 ؉ T cells from immunocompetent donors protected SCID mice infected with E. cuniculi, whereas administration of CD8 ؉ T cells from p40 ؊/؊ mice failed to protect infected SCID mice. In vitro dendritic cell (DC) cultures from knockout mice pulsed with E. cuniculi spores were unable to develop a robust CD8؉ T-cell immune response. Addition of exogenous IL-12 or transfer of CD8 ؉ T cells that were initially primed with DC from p40 ؊/؊ animals to DC cultures from immunocompetent mice (directly or via transwells) led to optimal expansion of these cells. This IL-12-mediated reinstatement of CD8 ؉ T-effector immunity was independent of gamma interferon (IFN-␥) as addition of antibody to the cultures failed to have an effect. These studies demonstrated that IL-12 plays a predominant role in the expansion of effector CD8 ؉ T-cell immunity against E. cuniculi, which is critical for host survival. These findings are very important for understanding the protective immune mechanisms needed to protect an immunocompromised host against an opportunistic infection and can be extended to other microsporidial pathogens.

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Lack of CD4⁺T Cells Does Not Affect Induction of CD8⁺T-Cell Immunity againstEncephalitozoon cuniculiInfection

Cited by 51 publications

References 39 publications

CD8⁺-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4⁺T Cells

CD8⁺-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4⁺T Cells

γδ T Cell-Deficient Mice Have a Down-Regulated CD8+ T Cell Immune Response AgainstEncephalitozoon cuniculiInfection

Lack of Interleukin-12 in p40-Deficient Mice Leads to Poor CD8⁺T-Cell Immunity againstEncephalitozoon cuniculiInfection

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Lack of CD4+T Cells Does Not Affect Induction of CD8+T-Cell Immunity againstEncephalitozoon cuniculiInfection

Cited by 51 publications

References 39 publications

CD8+-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4+T Cells

CD8+-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4+T Cells

γδ T Cell-Deficient Mice Have a Down-Regulated CD8+ T Cell Immune Response AgainstEncephalitozoon cuniculiInfection

Lack of Interleukin-12 in p40-Deficient Mice Leads to Poor CD8+T-Cell Immunity againstEncephalitozoon cuniculiInfection

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Lack of CD4⁺T Cells Does Not Affect Induction of CD8⁺T-Cell Immunity againstEncephalitozoon cuniculiInfection

CD8⁺-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4⁺T Cells

CD8⁺-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4⁺T Cells

Lack of Interleukin-12 in p40-Deficient Mice Leads to Poor CD8⁺T-Cell Immunity againstEncephalitozoon cuniculiInfection