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Cellular Mechanisms of Graft‐Versus‐Host Disease in a Mouse Model
Author(s) -
GIORGI L.,
LOWDELL M. W.,
MATOSSIANROGERS A.
Publication year - 1991
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1991.tb02527.x
Subject(s) - splenocyte , spleen , immunology , biology , mixed lymphocyte reaction , t lymphocyte , lymphocyte , immune system , offspring , in vitro , stimulation , ratón , microbiology and biotechnology , andrology , t cell , pregnancy , medicine , endocrinology , genetics , biochemistry
Female CBA/H (H‐2 k , Mls b ) mice alloimmunized prior to and during syngeneic pregnancy with DBA/2 (H‐2 d , Mls a ) splenocytes gave rise to offspring which resisted graft‐versus‐host disease (GVHD) following neonatal intraperitoneal inoculation of high doses of DBA/2 spleen cells. Lymphocytes from GVHD‐resistant mice tested after 6 weeks of age were unresponsive to DBA/2 stimulator cells in 72 h mixed lymphocyte cultures. Isotope uptake measured 24 h after culture, however, indicated that a considerable early response was made to DBA/2 which later declined. Proliferative responses to BALB/c were also depressed but no early response to this strain was detected. FACS analysis of T‐lymphocyte profiles of the GVHD‐resistant CBA/H mice revealed a 100% increase in the Lyt‐2 + subpopulation compared to normal CBA/H mice. Significant increases in Lyt‐2 + cells were also noted in in vitro cultures of CBA/H lymphocytes responding to GVHD‐resistant CBA/H stimulators. Lymphocytes from GVHD‐resistant mice suppressed the proliferative responses of normal CBA/H lymphocytes to alloantigenic but not mitogenic stimulation. Suppression of alloantigenic responses were shown to be specific to DBA/2 and did not affect the response to BALB/c stimulator cells, indicating that both anergy and specific suppressor cells were operative in inducing unresponsiveness.