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.