Mice lacking MHC class II molecules

Cosgrove, Dominic; Gray, David W.; Dierich, Andrée; Kaufman, Jim; LeMeur, Marianne; Benoist, Christophe; Mathis, Diane

doi:10.1016/0092-8674(91)90448-8

Cited by 822 publications

(578 citation statements)

References 93 publications

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“…The following mice were used between 6 and 12 wk of age: BALB/c (H-2 d ), B6 (H-2 b ), B6.CH-2 bm-1 (bm-1), MHC II-deficient [21] and the transgenic strains OT-I [22], OT-II [23], CL4 [24], HNT [25], CD11c:OVA [26] and TNF-a-deficient [27]. Mice were bred and maintained under specific pathogen-free conditions following institutional guidelines.…”

Section: Micementioning

confidence: 99%

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

et al. 2010

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Despite extensive evidence that Plasmodium species are capable of stimulating the immune system, the association of malaria with a higher incidence of other infectious diseases and reduced responses to vaccination against unrelated pathogens suggests the existence of immune suppression. Recently, we provided evidence that blood-stage Plasmodium berghei infection leads to suppression of MHC class I-restricted immunity to third party (non-malarial) antigens as a consequence of systemic DC activation. This earlier study did not, however, determine whether reactivity was also impaired to MHC class II-restricted third party antigens or to Plasmodium antigens themselves. Here, we show that while P. berghei-expressed antigens were presented early in infection, there was a rapid decline in presentation within 4 days, paralleling impairment in MHC class I-and II-restricted presentation of third party antigens. This provides important evidence that P. berghei not only causes immunosuppression to subsequently encountered third party antigens, but also rapidly limits the capacity to generate effective parasite-specific immunity.Key words: Antigen presentation . DC . Parasitic-Protozoan . Rodent . T cells IntroductionDespite extensive evidence that Plasmodium species are capable of stimulating the immune system, numerous studies have described immune suppression associated with infection, suggesting that Plasmodium parasites subvert immunity to promote persistence [1][2][3][4][5]. Various mechanisms have been suggested to underlie such suppression, including induction of CD4 1 T-cell apoptosis [6][7][8], suppression of DC function [9][10][11][12], or the generation of suppressive cytokines [1]. The observed humoral and cell-mediated immunity to malaria is, however, hard to reconcile with evidence of immune suppression, but may be explained by the ability of suppressive mechanisms to reduce but not completely prevent induction of immunity.Recently, we provided evidence that blood-stage Plasmodium berghei infection leads to suppression of MHC class I (MHC I)-restricted immune responses as a consequence of apparently normal DC activation [13]. While DC in infected mice were 1674shown to be fully competent in their ability to cross-present cellular antigens to CD8 1 T cells, provided they expressed antigen-MHC complexes on the surface, their activation phenotype led to a failure to capture newly encountered antigenic material and thus a failure to present such antigens [13]. In this case, DC were not directly suppressed but merely followed their normal maturation pathway after encounter with activatory stimuli. The net effect, however, was one of rapid, generalised immunosuppression because as the systemic infection progressed, all DC became activated, leaving no immature DC to capture subsequently encountered antigens.While systemic DC activation by P. berghei explained the reduced reactivity to subsequently encountered third party (nonmalarial) MHC I-restricted antigens, this earlier study did not determine whether reactivity...

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Section: Micementioning

confidence: 99%

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

et al. 2010

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“…C57BL/6J (normal B6) mice, B6 MHC-II -/-(A § -/-or A g -/-) mice [40][41][42] and C57BL/6J-Rag1 tm1Mom (RAG1 -/-) mice [43] (Jackson Labs; stock no. 2216) were used.…”

Section: Micementioning

confidence: 99%

MHC class II‐independent CD25⁺ CD4⁺ CD8α β⁺ α β T cells attenuate CD4⁺ T cell‐induced transfer colitis

2004

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CD4 + § g T cell populations that develop in mice deficient in MHC class II (through 'knockout' of either the A § , or the A g chain of the I-A b molecule) comprise a major 'single-positive' (SP) CD4 + CD8 -subset (60-90%) and a minor 'double-positive' (DP) CD4 + CD8 § g + subset (10-40%). Many DP T cells found in spleen, mesenteric lymph nodes (MLN) and colonic lamina propria (cLP) express CD25, CD103 and Foxp3. Adoptive transfer of SP but not DP T cells from A § -/-or A g -/-B6 mice into congenic RAG -/-hosts induces colitis. Transfer of SP T cells repopulates the host with only SP T cells; transfer of DP T cells repopulates the host with DP and SP T cells. Anti-CD25 antibody treatment of mice transplanted with DP T cells induces severe, lethal colitis; anti-CD25 antibody treatment of mice transplanted with SP T cells further aggravates the course of severe colitis. Hence, regulatory CD25 + T cells within (or developing from) the DP T cell population of MHC class II-deficient mice control the colitogenic potential of CD25 -CD4 + T cells.

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“…The generation of transgenic mice expressing different HLA class II alleles and lacking their endogenous class II MHC molecules has been described in detail elsewhere (32). Briefly, these mice do not carry functional endogenous class II MHC genes because of a spontaneous mutation in the promoter region of the H-2Ea gene (in H-2 b haplotypes), a defect which was then combined with a targeted disruption of the H-2A␤ gene (A␤ 0 knockout) (31). The original 4 transgenic lines used for the initial studies were HLA-DR2.Ab 0 (DRB1*1502) (33), HLA-DR3.Ab 0 (DRB1*0301) (34), HLA-DR4.Ab 0 (DRB1*04001) (35), and HLA-DQ8.Ab 0 (DQA1*0301 coexpressed with DQB1*0302) (36).…”

Section: Methodsmentioning

confidence: 99%

“…The polymerase chain reaction was used to screen genomic DNA from all mice for the presence of pertinent HLA class II transgenes and the neomycin resistance (Neo r ) gene disrupting the mouse H-2A locus (31). Cell surface expression of human class II MHC antigens was confirmed by flow cytometry of peripheral blood leukocytes.…”

Section: Methodsmentioning

confidence: 99%

“…To address whether human cartilage PG can be presented to mouse T cells in the context of the RApredisposing HLA-DR4 and/or HLA-DQ8 class II alleles and to determine whether any of the core protein epitopes of the human PG can induce arthritis in the presence of either a resistant or susceptible genetic background, we generated transgenic mice that express the human alleles but lack their own class II antigens (A␤ 0 knockouts [or, Ab 0 ]) (31). In the present study, we mapped all predicted T cell epitopes of PG that can be presented by the most frequent predisposing alleles in RA and found that, on an appropriate genetic background, human cartilage PG was arthritogenic in BALB/c mice that were transgenic for HLA-DR4.Ab 0 and HLA-DQ8.Ab 0 .…”

mentioning

confidence: 99%

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Induction of arthritis in HLA–DR4–humanized and HLA–DQ8–humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non‐MHC) genetic background

Szántó¹,

Bárdos²,

Szabó³

et al. 2004

Arthritis & Rheumatism

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Mice lacking MHC class II molecules

Cited by 822 publications

References 93 publications

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

MHC class II‐independent CD25⁺ CD4⁺ CD8α β⁺ α β T cells attenuate CD4⁺ T cell‐induced transfer colitis

Induction of arthritis in HLA–DR4–humanized and HLA–DQ8–humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non‐MHC) genetic background

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Mice lacking MHC class II molecules

Cited by 822 publications

References 93 publications

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

MHC class II‐independent CD25+ CD4+ CD8α β+ α β T cells attenuate CD4+ T cell‐induced transfer colitis

Induction of arthritis in HLA–DR4–humanized and HLA–DQ8–humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non‐MHC) genetic background

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MHC class II‐independent CD25⁺ CD4⁺ CD8α β⁺ α β T cells attenuate CD4⁺ T cell‐induced transfer colitis