Different strains of donor parental lymphoid cells induce different models of chronic graft-versus-host disease in murine (Balb/c × A/J)F1 hybrid hosts

Carmen Gelpi, M. Angeles Martinez, Silvia Vidal, Ana Algueró, Cándido Juarez, John A. Hardin, Jose Luis Rodriguez-Sanchez

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Abstract

The induction of a chronic graft-versus-host (cGVH) disease in (Balb/c × A/J)F1 mice by the intravenous injection of either Balb/c or A/J parental lymphoid cells led to the development of two different models of disease. In this paper we compared the clinical aspects and the antigen specificities which recognized the autoantibodies developed by the animals of these two models of cGVH disease. Renal disease, alopecia, and purpura lesions were common in both models, although their frequency and intensity varied between groups. The models were differentiated by two main characteristics. When donor cells were of Balb/c origin, a joint disease similar to rheumatoid arthritis developed in 50% of the animals, and when donor cells were of A J origin, 25% of the animals developed edema of the front feet, occasionally with loss of the nails, similar to that of scleroderma. Differences among the autoantibodies found in the sera of these two groups of mice were also observed. After the injection of Balb/c lymphoid cells, rheumatoid factors reactive with human and murine IgG were characteristically present (69 and 75%, respectively) and a statistically significant correlation was found between high titers of rheumatoid factor and arthritis (P < 0.001). Antinuclear antibodies (ANAs) were present in all animals. Anti-dsDNA and anti-histones were positive in 50 and 25%, respectively. Anti-snRNP were detected at a low titer in 35% of the animals. When donor cells were of A J origin, ANAs were also present in all mice. Anti-dsDNA, anti-histones, and anti-snRNPs antibodies were present in 90, 15, and 65%, respectively. The most outstanding characteristics among anti-snRNPs were the high titers of anti-U1 and anti-U3 detected in 50 and 30%, respectively. Rheumatoid factors reactive with human and murine IgG were positive in 15 and 42% of animals, respectively, but no significant correlation was found between these factors and disease. Our results indicate that the graft-versus-host disease induced in the same F1 strain of mice can be manifested in different forms of connective tissue disease, depending on whether the cells come from one or the other of the parental strains. Furthermore, in this paper the occurrence of rheumatoid factors in mice with cGVH is described for the first time.

Original languageEnglish (US)
Pages (from-to)298-310
Number of pages13
JournalClinical Immunology and Immunopathology
Volume56
Issue number3
DOIs
StatePublished - Sep 1990

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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