Intestinal graft-versus-host disease is initiated by donor T cells distinct from classic cytotoxic T lymphocytes.
In these studies, the role of T helper and T cytotoxic cells in generating intestinal graft-vs.-host disease (GVHD) was examined. Treatment of C57BL/6J (B6) splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte (CTL) precursors, and the capacity to cause lethal GVHD in irradiated B6xDBA/2 F1 (B6D2F1) mice while preserving T helper cell function. Neither control nor Leu-Leu-OMe-treated DBA/2 donor spleen and bone marrow cells were found to induce lethal GVHD in B6D2F1 recipients. However, extensive colonic GVHD developed in B6D2F1 recipients of DBA/2 bone marrow and spleen cells. Enteropathic GVHD in DBA/2----B6D2F1 mice was reduced in severity after anti-L3T4 + C treatment of donor cells, and was eliminated by anti-Thy1.2 + C or the combination of anti-L3T4 and anti-Lyt2 + C treatment of the donor cell inoculum. However, neither anti-Lyt2 + C, Leu-Leu-OMe, nor anti-Lyt2 + C and Leu-Leu-OMe treatment of donor cells significantly decreased severity of gut GVHD. Leu-Leu-OMe treatment of DBA/2 or B6 SpC was comparably effective in preventing in vitro or in vivo generation of B6D2F1-specific CTL. These findings, therefore, demonstrate that histologically severe enteropathic GVHD does not require participation of CTL and is not always associated with high mortality rates.
Thiele
D L
DL
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Eigenbrodt
M L
ML
Bryde
S E
SE
Eigenbrodt
E H
EH
Lipsky
P E
PE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D000950:Antigens, Ly / Q000032:analysis / Q000276:immunology; D016026:Bone Marrow Transplantation; D003106:Colon / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents; D007410:Intestinal Diseases / Q000276:immunology* / Q000473:pathology; D007518:Isoantibodies / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D004151:Dipeptides; D007166:Immunosuppressive Agents; D007518:Isoantibodies; C035678:anti-Thy antibody; C045139:leucyl-leucine-methyl ester