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Persistence of pathogenic CD4+ Th1-like cells in vivo in the absence of IL-12 but in the presence of autoantigen
- Source :
- Europe PubMed Central
- Publication Year :
- 2001
-
Abstract
- Despite recent successful treatment of murine autoimmune disease with anti-IL-12 mAb, it has not yet been addressed whether anti-IL-12 mAb can also be effective in late stages of disease and whether it can provide lasting protection against recurrence, especially during continued presence of autoantigen. We used a newly developed psoriasis model in scid/scid mice, which allows easy tracking of pathogenic T cells, to show that when anti-IL-12 mAb is given for 2 wk (1 mg/wk) in the late stage of severe disease, inflammation is greatly reduced, as measured by ear thickness and histology (scores, 1.1 ± 0.1 vs 2.0 ± 0.4). Moreover, prolonged treatment (4 wk) of chronic psoriatic mice with high doses of mAb (1 mg/wk; prolonged active anti-inflammatory treatment (PAAIT)) results in the almost complete resolution of lesions (scores, 0.3 ± 0.1 vs 2.7 ± 0.2). Surprisingly, however, despite these significant treatment results, the psoriasis-like lesions return soon after the anti-IL-12 mAb treatment is discontinued. This rapid relapse of disease may be attributed to large populations of activated CD4+ T cells present in the lymph nodes of PAAIT animals still expressing an effector/memory phenotype (CD45RBlow, L-selectinlow). Upon stimulation in vitro such PAAIT lymph node cells secrete high amounts of IFN-γ (129 ng/ml); when transferred into naive scid/scid animals they are able to rapidly induce disease without costimulation. Our data indicates an alternative IL-12-independent pathway for pathogenic Th-1-like cells in vivo during the chronic phase of disease that allows these cells to persist and maintain their pathogenicity in the draining lymph tissue of the autoimmune site.
- Subjects :
- CD4-Positive T-Lymphocytes
Adoptive cell transfer
Cell Survival
Immunology
Inflammation
Mice, SCID
Biology
Autoantigens
Lymphocyte Depletion
Mice
In vivo
Recurrence
T-Lymphocyte Subsets
medicine
Immunology and Allergy
Animals
Psoriasis
Lymph node
Immunization Schedule
Autoimmune disease
Mice, Inbred BALB C
Anti-Inflammatory Agents, Non-Steroidal
Antibodies, Monoclonal
Th1 Cells
medicine.disease
Adoptive Transfer
Interleukin-12
Disease Models, Animal
medicine.anatomical_structure
Chronic Disease
biology.protein
Interleukin 12
Female
Lymph
Lymph Nodes
medicine.symptom
Antibody
Injections, Intraperitoneal
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 166
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....b8b865a09b7e661f6925c9c9fecbf51f