Comparative effects of various T cell subtypes on GVHD in a murine model for MHC-matched unrelated donor transplant.
Studies were undertaken to achieve a further understanding of T cell subtype involvement in minor-histocompatibility graft-versus-host disease (MiHL-GVHD) as it may occur in MHC-matched unrelated donor (MUD) transplantation. For this, the H-2 identical, but minor-histocompatibility disparate, B10.S----SJL/J mouse model was employed, using a 50/50 mixture of B10.S spleen and marrow cells to induce GVHD in the SJL/J recipients. Utilizing dual labeling flow cytometry analysis, the relative distributions of the various T cell subtypes within the spleen and marrow of the B10.S donor strain were determined. The effects of selectively depleting for pan-T (Thy-1+), CD-4 (L3T4+), CD-8 (Lyt-2+), or CD-5 (Lyt-1+) cells were then evaluated and the results were compared with the incidence and severity of GVHD in the recipients. The data reinforced the results of previous studies indicating that a significant element of MiHL-GVHD is dependent on CD-8 cytolytic T cells which may operate independently of any helper cell input. However, they also indicated that the presence of CD-4 helper cells can accelerate the response. Furthermore, they suggested that the induction of MiHL-GVHD in MUD transplants may not be limited to the activity of fully matured T cells, but that other immature T cell subtypes, lacking in both the CD-4 and CD-8 markers, may likewise be involved.
Cancer Research Laboratories, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212.
J P
JP
OKunewick
D L
DL
Kociban
M J
MJ
Buffo
D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018956:CD5 Antigens; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D007518:Isoantibodies / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000637:transplantation*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018800:Thy-1 Antigens
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018956:CD5 Antigens; D007518:Isoantibodies; D015778:Minor Histocompatibility Antigens; D018800:Thy-1 Antigens; C035678:anti-Thy antibody