CD3+ T cells in severe combined immunodeficiency (scid) mice. II. Transplantation of dm2 lymphoid cells into semi-allogeneic scid mice.

Intravenous injection of nonfractionated BALB/c-H-2dm2 (dm2) (Ld−) spleen cells into 4-week-old, semi-allogeneic (H-2d, Ld+) C.B-17 scid/scid severe combined immunodeficient (scid) mice (2 × 107 cells/mouse) reconstituted T lymphopoiesis in thymi and repopulated the lymphoid white pulp in spleens of these immunodeficient recipients. Transplantation of dm2 thymocytes into young scid mice (5 × 107 cells/mouse) established a donor-derived CD3+ T cell population in spleens of recipient scid mice, in which CD4+ T cells predominated. This was demonstrated by marker analyses of thymocytes and splenocytes, and determinations of serum immunoglobulin levels in transplanted scid mice. Transfer of splenocytes from young primary scid recipients into young secondary or tertiary recipients (3 × 106 cells/mouse) engrafted preferentially dm2-derived CD3+CD4+CD8− T cells in spleens of scid mice despite the strong selective Ld-associated alloantigenic stimulus for CD8+ T cells. Intravenous injections of nonfractionated dm2 spleen cells (2 × 107 cells/mouse) or thymocytes (5 × 107 cells/mouse) into 10- to 12-month-old, “leaky” scid mice induced severe clinical signs of graft-vs.-host disease (GVHD) in all scid recipients. Lymphoid repopulation of spleen and thymus in old scid recipients was incomplete. This GVHD was not transferrable by injecting 3 × 106 spleen cells from old diseased primary scid recipients into secondary or tertiary young scid recipient mice. In these serial transfers, dm2-derived CD3+CD4+CD8− T cells were again preferentially engrafted in spleens of scid recipients. Transfer of purified CD4+ dm2 T cells into young scid mice (2 × 105 to 5 × 105 cells/mouse) engrafted this T cell subset into the spleen of semi-allogeneic scid recipients. This was revealed by histological examinations, surface marker analyses, in vitro isolation of donor-type CD3+CD4+ T cell lines from spleens of transplanted scid mice, and serial transfer experiments. These data indicated that the CD4+ T cell compartment of scid mice can be selectively repopulated by semi-allogeneic T cells. Injections of purified CD8+ dm2 T-cells into young scid mice (2 × 105 cells/mouse) did not establish a CD8+ T cell graft in spleens of recipients. It was necessary to inject transplanted scid mice biweekly with 104 units recombinant interleukin 2 to establish and/or maintain transferred dm2 CD8+ T cells in spleens of these recipients. dm2 CD8+ T cell-transplanted and interleukin 2-treated scid mice did not develop any evidence of GVHD over the 9-week observation period.