Vaccination with autoreactive CD4(+)Th1 clones in lupus-prone MRL/Mp-Fas(lpr/lpr) mice.
We studied the efficacy of T cell vaccination with CD4(+)alphabetaTh1 clones in lupus-prone MRL/Mp-Fas(lpr/lpr) (MRL/lpr) mice. CD4(+)alphabeta Th1 clones, dna51 (Vbeta8.3) and rnp2 (Vbeta14), 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(+)Vbeta8.3 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 Vbeta8.3-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(+)alphabetaTh1 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.
Fujii
Takao
T
Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan. takfujii@kuhp.kyoto-u.ac.jp
Okada
Masato
M
Fujita
Yoshimasa
Y
Sato
Takeshi
T
Tanaka
Masao
M
Usui
Takashi
T
Umehara
Hisanori
H
Mimori
Tsuneyo
T
D019264:Adoptive Transfer; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D005260:Female; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology; D018417:Th1 Cells / Q000637:transplantation*; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D017412:Ribonucleoprotein, U1 Small Nuclear