The Neonatal CD4+ T Cell Response to a Single Epitope Varies in Genetically Identical Mice.

Neonatal infection is a major cause of morbidity and mortality worldwide. Increased susceptibility to infection in the neonate is attributed in part to defects in T cell-mediated immunity. A peptide:MHC class II tetramer-based cell enrichment method was used to test this hypothesis at the level of a single epitope. We found that naive T cells with TCRs specific for the 2W:I-A(b) epitope were present in the thymuses of 1-d-old CD57BL/6 mice but were barely detectable in the spleen, likely because each mouse contained very few total splenic CD4(+) T cells. By day 7 of life, however, the total number of splenic CD4(+) T cells increased dramatically and the frequency of 2W:I-A(b)-specific naive T cells reached that of adult mice. Injection of 2W peptide in CFA into 1-d-old mice generated a 2W:I-A(b)-specific effector cell population that peaked later than in adult mice and showed more animal-to-animal variation. Similarly, 2W:I-A(b)-specific naive T cells in different neonatal mice varied significantly in generation of Th1, Th2, and follicular Th cells compared with adult mice. These results suggest that delayed effector cell expansion and stochastic variability in effector cell generation due to an initially small naive repertoire contribute to defective peptide:MHC class II-specific immunity in neonates.

Severe paediatric systemic lupus erythematosus nephritis--a single-centre experience.

BACKGROUND: Paediatric patients with systemic lupus erythematosus (SLE) often have severe presentations including lupus nephritis (LN). Few paediatric studies have evaluated the anticardiolipin antibody (aCL) and renal histology. The purpose of this study was to evaluate clinicopathologic features, including aCL, short-term clinical and renal histologic outcomes of paediatric patients with new-onset SLE nephritis. METHODS: We conducted a single centre, retrospective inception cohort study. Charts were reviewed at presentation (initial renal biopsy), 6-month (follow-up biopsy) and 12-month follow-up. RESULTS: The population consisted of 21 patients (median age, 14.5 years): 19/21 were female, 6/21 African American, 3/21 Asian, 9/21 Caucasian and 3/21 Hispanic. At presentation, 19/21 had elevated aCL, 15/21 hypertensive, 12/21 nephrotic and 7/21 required haemodialysis (HD)-2/7 HD patients had thrombotic microangiopathy, 1/7 crescentic glomerulonephritis. Two patients had thromboembolism: both had aCL, were taking oral contraceptives and required HD, one was nephrotic and the other had elevated lupus anticoagulant. Initial biopsies revealed 6/21 ISN/RPS class II nephritis, 3/21 class III, 7/21 class IV and 5/21 class V. Treatment consisted of methylprednisolone, corticosteroids, cyclophosphamide or mycophenolate mofetil. Follow-up biopsies revealed 12/13 to have improved histology. Indication for a follow-up biopsy was severe illness at presentation. At 12-month follow-up, no patients were nephrotic (P < 0.001) or required HD (P < 0.001), and 3/14 had elevated aCL (P < 0.001). CONCLUSION: Elevated aCL, hypertension, nephrotic syndrome and need for HD were common presentations among our paediatric SLE nephritis population. Renal histology and aCL were helpful in the therapeutic management.