Vaccination with autoreactive CD4 +Th1 clones in lupus-prone MRL/Mp- Fas lpr/lpr mice

Abstract

We studied the efficacy of T cell vaccination with CD4 +αβTh1 clones in lupus-prone MRL/Mp- Fas lpr/lpr (MRL/ lpr) mice. CD4 +αβ Th1 clones, dna51 (Vβ8.3) and rnp2 (Vβ14), which stimulated anti-dsDNA or U1 ribonucleoprotein (U1RNP) antibody (Ab) production respectively, were isolated from splenocytes of MRL/ lpr mice. Antinuclear Ab kinetics, renal function, renal histology, survival rate, and lymphocyte subpopulations in the spleen were monitored after intravenous adoptive transfer of IL-2-stimulated (s-) or irradiated (i-) clones to 3 week-old female MRL/ lpr mice. Anti-idiotypic humoral and T cell responses against the transferred autoreactive Th1 clones were determined in parallel. Compared with PBS-treated MRL/ lpr mice, anti-dsDNA Ab titers, and the activity index for lupus nephritis were all decreased in MRL/ lpr mice vaccinated with i-dna51 cells, whereas survival rate was not improved. The numbers of CD4 +Vβ8.3 T cells in the spleen were also significantly decreased in these mice. Anti-idiotypic Abs recognizing a 12 amino acid sequence of clone dna51 T cell receptor Vβ8.3-complementarity-determining region (CDR) 3 were detected in the MRL/ lpr mice that received i-dna51 or s-dna51 cells. These Abs suppressed dna51 cell proliferation, as well as cytotoxicity of CD8 +T cells against dna51. The present study suggests that vaccination with CD4 +αβTh1 clone, dna51, elicits anti-idiotypic T cell and humoral responses against dna51 in MRL/ lpr mice, although the immunoregulatory effects on lupus may be limited.