The Adoptive Transfer of First‐set Allograft Responses by Recirculating Small Lymphocytes in the Rat

Abstract

Summary. While the immunological competence of recirculating, small lymphocytes in the thoracic duct lymph is well documented, there is no unequivocal evidence that these are the cells which mediate the rejection of first-set allografts in vivo. This evidence was sought by assaying the capacity of thoracic duct lymphocytes from normal donors to adoptively restore primary skin ailograft responses to recipients in which these responses had been suppressed by irradiation. It was found that 30 million thoracic duct lymphocytes were sufficient to restore rejection of allogeneic skin with a normal first-set tempo. The cell type responsible was identified as the recirculating small lymphocyte by showing that those cells which migrated from blood to lymph in heavily irradiated syngeneic rats were equally competent to restore first-set ailograft responses. The specificity of this restoration was shown using thoracic duct lymphocytes from tolerant donors which restored activity against third party allo-antigens but not against antigens of the strain to which the donor was tolerant. These results establish that recirculating small lymphocytes mediate the destruction of first-set aUografted tissue in vivo.

Recirculating, suppressor T cells in transplantation tolerance.

“…Adoptive Restoration of Allograft Reactivity to Irradiated Rats. The details of the adoptive allograft assay have been previously reported (23). Assay animals were irradiated with 750 rads and 24 h later grafted with two mutually Ag-B disparate skin grafts and injected intravenously (i.v.)…”

A Quantitative Lymph Node Weight Assay for Allogeneic Interactions in the Rat

“…Thus, the response of tolerant animals to the tolerated antigen did not differ from the response to syngeneic cells (3-7 ± 0-2 mg). Doses of y irradiation known to suppress the skin allograft response (Dorsch and Roser, 1974a) also abolished the lymph node response. In DA rats irradiated with 750 rads cobalt y irradiation and challenged in the RFP with 2 x 10' (DA x HO)F, TDL the challenged node weighed 1-8 mg, compared with 1-3 mg for the contraluteral node.…”

“…Especially where differences at major histocompatiliilit)' loci are involved, the difference in graft survival times between normal and sensitized ho.sts can l)e very small (Hildemann, 1970). In the rat, Ag-B disparate, first-set skin graft.s are rejected promptly in 8 or 9 days (Roser and Ford, 1972;Dorsch and Roser, 1974a) and prior sensitization may reduce this survival time by less than 24 h, so that skin allografts are poor indicators of a state of immunity in this species.…”

“…Especially where differences at major histocompatiliilit)' loci are involved, the difference in graft survival times between normal and sensitized ho.sts can l)e very small (Hildemann, 1970). In the rat, Ag-B disparate, first-set skin graft.s are rejected promptly in 8 or 9 days (Roser and Ford, 1972;Dorsch and Roser, 1974a) and prior sensitization may reduce this survival time by less than 24 h, so that skin allografts are poor indicators of a state of immunity in this species. SUSAN E. DORSCII AND BRUCE ROSER The uniform lack of success, ii.siug skin allograft assays, in demonstrating the expected dose-response relationships characteristic of all other immune assays (Hildemann, 1970) is a serious obstacle to the use of skin allografts in the precise analysis of the character and function of transplantation antigens, where a quantitative assay would be extremely valuable.…”

The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts.

“…However, the association of a particular immune response with graft rejection does not necessarily imply that it is a requirement for rejection (5). The cellular requirements for graft rejection in vivo can be directly established by adapting the adoptive transfer technique (7) and testing known cell populations singly or in combination for their ability to cause rejection in irradiated animals bearing allografts (8)(9)(10).…”