Enhancement of BM allografting from C57BL/6 'nude' mice into C3H/HeJ recipients by tolerized T cells from (C57BL/6-->C3H/HeJ) and (C3H/HeJ-->C57BL/6) chimeras.

The possible participation of T cells in the promotion of hematopoietic engraftment of BM allografts, as opposed to their potential role in overcoming host-versus-graft reactions, was investigated recently by using (host x donor)F1 T cells devoid of graft-versus-host activity. In the present study, we provide further evidence of this effect by using tolerized thymocytes from established allogeneic chimeras. We show that tolerant mature thymocytes from donor type (C57BL/6-->C3H/HeJ) or host type (C3H/HeJ-->C57BL/6) chimeras are as effective as (donor x host)F1 thymocytes in promoting both short-term and long-term engraftment of C57BL/6-Nu/Nu T cell-depleted BM cells in lethally irradiated C3H/HeJ recipients.

Enhancement of T-cell-depleted bone marrow allografts in the absence of graft-versus-host disease is mediated by CD8+ CD4- and not by CD8- CD4+ thymocytes.

Transplantation of T-cell-depleted C57BL/6-Nu/Nu ("nude") bone marrow (BM) into C3H/HeJ recipients, conditioned with 8 Gy total body irradiation plus chemotherapy with the myeloablative drug dimethyl myleran, resulted in poor hematopoietic reconstitution 14 days posttransplant, compared with transplantation with T-cell-depleted BM from normal C57BL/6 donors. Hematopoietic reconstitution of "nude" BM could be improved by the addition of (C57BL/6xC3H/HeJ)F1 thymocytes void of graft-versus-host activity. Enhancement of BM allografting by thymocytes is sensitive to low radiation doses (> or = 5.0 Gy) and can be achieved by transplanting the BM 24 hours before the administration of thymocytes. Fractionation of F1 thymocytes by differential agglutination with peanut agglutinin (PNA) and by fluorescence activated cell sorting showed that this hematopoietic enhancing activity is enriched in the unagglutinated (PNA-) thymocyte fraction and is mediated by PNA- CD8+ and not by PNA- CD4+ thymocytes.

Engraftment and development of human T and B cells in mice after bone marrow transplantation.

A model for human lymphocyte ontogeny has been developed in a normal mouse. Human bone marrow, depleted of mature T and B lymphocytes, and bone marrow from mice with severe combined immunodeficiency were transplanted into lethally irradiated BALB/c mice. Human B and T cells were first detected 2 to 4 months after transplantation and persisted for at least 6 months. Most human thymocytes (30 to 50 percent of total thymocytes) were CD3+CD4+CD8+. Human immunoglobulin was detected in some chimeras, and a human antibody response to dinitrophenol could be generated after primary and secondary immunization.

Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity.

Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells.