Lack of GVHD across classical, single minor histocompatibiliTy (miH) locus barriers in mice.
To determine whether a disparity at a single miH genetic loci are sufficient to generate GVHD in mice, we focused on well-known genetic alleleic differences at the miH gene loci, H3 and H4. For H3 congenic GVHD studies, C57BL/10 (H2b) mice were used as recipients of miH-disparate B10.LP-H3b donor cells. For H4 congenic GVHD studies, C57BL/10 were used as recipients for miH-disparate B10.129 (21M)-H4b. To overcome the low frequency of miH-reactive CTLs in naive mice, multiple immunizations of the donor strains with host lymphohematopoietic cells were used. Peripheral blood cells from immunized mice were shown to have potent CTL activity against their respective host-type stimulator cells when analyzed 1 week prior to obtaining donor splenocytes for GVHD induction. Lethally irradiated C57BL/6 recipients of either 50 X 10(6) donor B10.LP-H3b or B10.129 (21M)-H4b splenocytes did not develop acute or chronic GVHD as assessed by monitoring the animals for survival, weight loss, splenic flow cytometry, and histological examination of skin, liver, colon, and lung in long-term survivors. Engraftment was documented in long-term chimeras in both strain combinations by using the post-BMT cells as alloantigen targets for cloned CTL lines specific for donor and not host-type miH antigens (H3b or H4b). On day 6 post-BMT, donor antihost CTL activity could not be detected in the spleen, although third-party responses were intact. These results suggest a rapid downregulation or disappearance of miH antigen-reactive CTL after BMT. These data have implications for the use of in vitro assays to predict GVHD risk in recipients of miH loci-disparate donor grafts.
Blazar
B R
BR
Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota Hospital and Clinic, Minneapolis 55455, USA.
Roopenian
D C
DC
Taylor
P A
PA
Christianson
G J
GJ
Panoskaltsis-Mortari
A
A
Vallera
D A
DA
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D017690:Cell Transplantation; D006086:Graft vs Host Disease / Q000276:immunology*; D007114:Immunization; D007519:Isoantigens / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D008912:Minor Histocompatibility Loci / Q000276:immunology*; D012307:Risk Factors; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014916:Whole-Body Irradiation
D007519:Isoantigens; D015778:Minor Histocompatibility Antigens