Generation of cytotoxic T cell responses directed to human leucocyte antigen Class I restricted epitopes from the<i>Aspergillus</i>f16 allergen

Ramadan, Gamal; Davies, B.; Kurup, Viswanath P.; Keever-Taylor, Carolyn A.

doi:10.1111/j.1365-2249.2005.02738.x

Cited by 44 publications

(42 citation statements)

References 59 publications

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“…Both CD4 ϩ T cells [13][14][15] and CD8 ϩ T cells 13,25,41 are present in the murine and human T-cell repertoire to the fungus. However, the role of CD8 ϩ T cells in infection, the specific fungal Ags they recognize, and mechanisms underlying their activation are unknown.…”

Section: Discussionmentioning

confidence: 99%

“…24 In the first model, mice were injected intranasally with 2 ϫ 10 7 conidia/20 L of saline 14 days before the infection or with 5 g of the A fumigatus cell wall glucanase Crf1p, which is known to induce MHC class II-restricted memory antifungal CD4 ϩ Th1 responses 13,25 together with 10nM CpG in 20 L of saline administered 14, 7, and 3 days before the infection. Mice were immunosuppressed IP with 150 mg/kg of cyclophosphamide 1 day before the infection.…”

Section: Vaccination Modelsmentioning

confidence: 99%

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TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Carvalho

Luca

Bozza

et al. 2012

Blood

117

122

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Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8 ؉ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8 ؉ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4 ؉ and CD8 ؉ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHCrestricted, CD8 ؉ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8 ؉ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8 ؉ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients. IntroductionTLR3 plays a key role in modulating inflammation and innate immunity in the airway. Although best known for recognition of viral double-stranded RNA (dsRNA) and its synthetic analog polyinosinic:polycytidylic acid [poly(I:C)], 1 TLR3 also recognizes endogenous ligands, 2 including heterologous RNA released from or associated with necrotic cells or generated by in vitro transcription. 3 Therefore, TLR3, together with other intracellular signaling proteins, 4 induces or otherwise modulates innate immune responses and inflammation in settings that are not associated with viral dsRNA. TLR3 signaling may also modulate adaptive immune responses by providing cross-priming of cytotoxic T lymphocytes through signaling in dendritic cells (DCs) 5,6 via type I IFNs 7 and in the absence of CD4 ϩ T-cell help. 8 Therefore, it is not surprising that people with mutations in key TLR3 signaling components have a selective immunodeficiency manifested by recurrent episodes of herpes simplex virus 1 encephalitis 9,10 or enteroviral myocarditis/cardiomyopathy. 11 Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. Humans inhale hundreds of conidia every day without adverse consequences, 12 except for a minority of persons in whom defense systems fail and a life-threatening form of disease can develop. CD4 ϩ and CD8 ϩ T cells are present in the human T-cell repertoire to the fungus 13-15 and adoptive transfer of A fumigatus-specific CD4 ϩ T cells conferred protection against invasive fungal infection. 15,16 Recent studies indicate a role for TLR3 in murine aspergillosis. By functioning as an endogenous sensor of fungal RNA, 17 TLR3 mediates expression of the enzyme indoleamine 2,3-dioxygenase (IDO) on both epithelial cells 18 and DCs,19 contributing to the local regulation of innate and adaptive inflammation to the fungus. However, the findings that protective memory CD8 ϩ T cells are induced against fungi 20-23 suggest a possible rol...

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Section: Discussionmentioning

confidence: 99%

Section: Vaccination Modelsmentioning

confidence: 99%

TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Carvalho

Luca

Bozza

et al. 2012

Blood

117

122

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“…[17][18][19] The demonstration that CD8 ϩ Mucorales-specific T cells may produce either IL-4 or IL-10, predominantly in the late phase of the infection, is reminiscent of the type 2 cytokine shift of CD8 ϩ lymphocytes, thus far reported only in patients with the cavitary phase of tuberculosis and in the late phase of HIV infection. 20,21 In conclusion, Mucorales-specific T cells emerge in the course of IM and contribute to human immune responses against Mucorales.…”

Section: Discussionmentioning

confidence: 99%

Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients

Potenza

Vallerini

Barozzi

et al. 2011

Blood

110

100

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Mucorales-specific T cells were investigated in 28 hematologic patients during the course of their treatment. Three developed proven invasive mucormycosis (IM), 17 had infections of known origin but other than IM, and 8 never had fever during the period of observation. Mucorales-specific T cells could be detected only in patients with IM, both at diagnosis and throughout the entire course of the IM, but neither before nor for long after resolution of the infection. Such T cells predominantly produced IL-4, IFN-γ, IL-10, and to a lesser extent IL-17 and belonged to either CD4+ or CD8+ subsets. The specific T cells that produced IFN-γ were able to directly induce damage to Mucorales hyphae. None of the 25 patients without IM had Mucorales-specific T cells. Specific T cells contribute to human immune responses against fungi of the order Mucorales and could be evaluated as a surrogate diagnostic marker of IM.

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“…One of the preferred alleles in the influenza A virus-specific cytotoxic-T-lymphocyte response is HLA-B*3501; preferential HLA usage is dependent on the type of the virus and determines differential cytokine expression (2, 3). The HLA-B*35 allele has also been associated with chronic hepatitis B virus, hepatitis C virus, and herpes simplex virus infections; Epstein-Barr virus seropositivity; and cytotoxic responses against Aspergillus and Mycobacterium tuberculosis (10,20,33,45). In human immunodeficiency virus infection, the rapid progression of the disease has been correlated to the interaction of a virus peptide with B*35 (4).…”

Section: ) Nsmentioning

confidence: 99%

Association of Chlamydia pneumoniae Infection with HLA-B*35 in Patients with Coronary Artery Disease

Palikhe

Lokki

Saikku

et al. 2008

Clin Vaccine Immunol

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The immune system may interplay between Chlamydia pneumoniae infection and coronary artery disease (CAD). Major histocompatibility complex genes regulate innate and adaptive immunity. Patients with CAD (n ‫؍‬ 100) and controls (n ‫؍‬ 74) were enrolled. Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred. The presence of serum C. pneumoniae immunoglobulin A (IgA) (titer, >40) or IgG (titer, >128) antibodies or immune complex (IC)-bound IgG antibodies (titer, >2) was considered to be a serological marker suggesting chronic C. pneumoniae infection. C. pneumoniae IgA antibodies were found more frequently in patients than in controls (P ‫؍‬ 0.04). Among the patients, multiple logistic regression analysis showed the HLA-B*35 allele to be the strongest-risk gene for C. pneumoniae infection (odds ratio, 7.88; 95% confidence interval, 2.44 to 25.43; P ‫؍‬ 0.0006). Markers of C. pneumoniae infection were found more frequently in patients with the HLA-A*03-B*35 haplotype than in those without the haplotype (P ‫؍‬ 0.007 for IgA; P ‫؍‬ 0.008 for IgG; P ‫؍‬ 0.002 for IC). Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes (P ‫؍‬ 0.003 and P ‫؍‬ 0.001, respectively). No associations were found in controls. In conclusion, HLA-B*35 may be the link between chronic C. pneumoniae infection and CAD.

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Generation of cytotoxic T cell responses directed to human leucocyte antigen Class I restricted epitopes from theAspergillusf16 allergen

Cited by 44 publications

References 59 publications

TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients

Association of Chlamydia pneumoniae Infection with HLA-B*35 in Patients with Coronary Artery Disease

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