Tumor-induced altered gastrointestinal steady-states: absence of MHC restriction in the paraneoplastic gastrointestine.
The growth of a number of experimental rodent tumours including the Lewis lung tumour (LLca) progressively compromises the integrity of the host's gastroinestine by inducing cytokinetic alterations in the small bowel resembling those generally defining the intestinal phase of a graft-versus-host reaction (GVHR). To determine whether the induction of this paraneoplastic gastrointestine (PGI) involves, similar to a GVHR, a disparity between the MHC of the donor (LLca tumour) and the recipient (host), PGI development was evaluated in various LLca tumour-bearing murine strains that were either 'syngeneic' [C57BL/6 and BL/10 (H-2b)], 'semisyngeneic' [B6D2F1 (H-2bd) and B6C3F1 (H-2bk)] or 'allogeneic' [C3H/HeJ (H-2k) and DBA/2 (H-2d)] to the H-2b LLca tumour. The temporal appearance and magnitude of a PGI developing in either LLca-syngeneic or semi-syngeneic hosts, but not the allogeneic strains, suggested that the mechanism(s) involved in PGI development like the GVHR, was restricted by the MHC. Subsequent studies using congenic strains [B10.A (H-2k) and B10.D2/nSn (H-2d)], however, demonstrated that the mechanism(s) responsible for the PGI was restricted by the non-MHC loci of the C57BL mouse. These observations were supported by the appearance of a LLca-induced PGI in various B10.A congenic strains carrying mutations at the I-A or I-E/I-J loci of the MHC. Not unlike the intestinal phase of a GVHR, development of the PGI required the participation of enhanced mucosal mast cells which were limited in the WCB6F1 (S1/S1d) but not the (+/+) murine strains. These observations are discussed in light of the postulated premature migration of immature thymocytes that accompany tumour growth and their ability to non-specifically enhance (or suppress) cell mediated immune reactions in the host.
Kovacs
C J
CJ
Division of Radiation Biology and Oncology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Evans
M J
MJ
Langweiler
M
M
Gould
B J
BJ
Gooya
J M
JM
D000818:Animals; D002277:Carcinoma / Q000473:pathology; D002455:Cell Division; D004064:Digestive System / Q000276:immunology / Q000473:pathology*; D006087:Graft vs Host Reaction; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology