The role of BALB/c donor CD8+ lymphocytes in graft-versus-host disease in (BALB/c x A/J)F1 (CAF1) mice.
To investigate the role of donor T lymphocyte subsets in the development of chronic graft-vs-host disease (GVHD) induced in (BALB/c x A/J)F1 (CAF1) mice by injecting BALB/c lymphoid cells, we analyzed the effect that CD8+ cell removal from donor inoculum has on the manifestation of the disease. Compared with age- and sex-matched CAF1 mice injected with whole lymphocyte inoculum, CAF1 mice injected with CD8(+)-depleted inoculum exhibited: 1) a higher incidence and exacerbation of nephritis by immunocomplexes; 2) higher (five- to sevenfold) spontaneous IL-4 production; 3) higher frequency titer and precocity of anti-dsDNA, anti-histone, and IgM and IgG rheumatoid factors; 4) a dramatic change in the frequency and titer of anti-U1 small nuclear ribonucleoprotein Abs; and 5) a markedly decreased engraftment (10- to 15-fold) on BALB/c donor lymphocytes. In contrast, rheumatoid arthritis-like disease, a later clinical manifestation of the GVHD in CAF1 + BALB/c model, is not present in the CD8(+)-depleted model (CAF1 + CD8-BALB/c). Considered together, these data suggest that CD8+ donor T lymphocytes play an important role in the degree of chimerism, modulation of the response to autoantigens, and clinical aspects developed in the GVHD model presented here.
Vidal
S
S
Department of Immunology, Hospital de Sant Pau, Universitat Autonoma de Barcelona, Avgda, Spain.
Labrador
M
M
Rodríguez-Sánchez
J L
JL
Gelpí
C
C
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002455:Cell Division / Q000276:immunology; D002678:Chimera / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology
D007376:Interleukin-2; D015847:Interleukin-4