Interactions between T lymphocyte subsets supported by interleukin 2-rich lymphokines produce acute rejection of vascularized cardiac allografts in T cell deprived rats.
A series of adoptive transfer studies were performed to define both the role of lymphocyte subpopulations and of lymphokines in the reestablishment of immunologic responsiveness towards vascularized organ allografts in T cell-deprived B rats. Acute rejection of otherwise indefinitely surviving cardiac allografts (10.9 +/- 2.9 days) occurred when sensitized T cells were adoptively transferred with a course of partially purified, lectin-free IL 2-conditioned medium (IL 2CM), whereas rats receiving T cells alone rejected their grafts at 19.8 +/- 4.6 days (p = 0.025). Rejection is mediated primarily by alloactivated T helper cells highly enriched for W3/25 phenotype. The relationship between the mean allograft survival time and the cell number transferred was of exponential order. In contrast to rejection occurring after the transfer of intact T cells, that produced by W3/25+ cells was independent of the administration of exogenous IL 2CM. W3/25+ T helper cells were also found to be less potent in mediating graft rejection than were whole T cells when limited cell numbers were transferred. The OX8+ T cytotoxic/suppressor cell subpopulation, even when supplied with a course of IL 2CM, was unable to bring about rejection, but induced transient graft enlargement in about 50% of the animals. Recombination of individual subsets caused acute rejection at a rate comparable to that of unseparated T cells when IL 2CM was supplied (10.8 +/- 1.0 days), in contrast to those rats which received the recombined inoculum in the absence of IL 2CM (16.8 +/- 2.2 days, p = 0.025). Lymphocyte migration studies revealed a more vigorous homing of OX8+ cells to the allograft as compared to W3/25+ cells. However, to produce maximal accumulation of transferred cells in the graft, both T cell subsets supplemented by lymphokines must be introduced together into T cell-deprived hosts.
D000818:Animals; D002465:Cell Movement; D003326:Coronary Circulation; D006084:Graft Rejection; D006321:Heart / Q000502:physiology; D016027:Heart Transplantation; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000502:physiology*; D008211:Lymphocyte Cooperation; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007376:Interleukin-2