Invasion and Destruction of Homologous Kidney by Locally Inoculated Lymphoid Cells

Abstract

There exists convincing evidence that vascularized homografts of solid tissues are destroyed by an immune reaction of the delayed hypersensitive type, and that the lymphocyte plays some crucial role in the genesis of such reactions (1--4). Infiltration by mononuclear inflammatory cells (lymphocytes and histiocytes) is a fundamental characteristic of primary homografts undergoing rejection (5-8), but the question remains as to the precise role which these mononuclear cells play in the destruction of the tissue they have infiltrated. Are they the agents which perpetrate the destruction or are they secondary invaders which have congregated in tissue already injured by some other agency?Recently a number of elegant experiments have shown that specifically sensitized lymphocytes cluster upon and destroy their intended target cells in vitro (9-11), so it does seem that lymphocytes are capable of killing antigenic cells with which they are in contact.The experiments described here and in a preliminary report (12) show that lymphoid cells possess a similar destructive capacity in vivo. The evidence consists of the demonstration that local inoculation of lymphoid cells from inbred parental strain donors is followed by the infiltration and destruction of renal parenchyma in F1 hybrid rats. It will be shown that this reaction develops when the immunogenetic conditions for unidirectional graft vs. host reactions (GVHR) have been met (13), so that humoral antibody and lymphoid cells of host origin cannot play a primary, immunologically specific role in the reaction. Additional experiments which confirm the nature of the observed reaction and which demonstrate the role of lymphocytes of donor origin in it are presented.

The Interaction of Donor and Host Lymphoid Cells in the Pathogenesis of Renal Cortical Destruction Induced by a Local Graft Versus Host Reaction

“…1 b and 2 b) were in fact due to propagation of the GVHR, and did not simply represent a nonspecific inflammatory response to the grafted necrotic tissue. Furthermore, the histopathology of the positive lesions in hybrid secondary hosts was almost identical with that in the primary hosts (8). The outer cortex contained an interstitial infiltrate of pleomorphic mononuclear inflammatory cells, including "blast" forms ( Fig.…”

“…1, the inoculation of lymphoid cells, which are for immunogenetic reasons incompetent to induce a GVHR in a given host, does not change the weight ratio of the injected/contralateral control kidney (Ki/Kc) from the expected value of 1. When, however, GVHR's are induced with competent inocula and the host autopsied after 7 days, this ratio (Ki/Kc) is elevated due to the tumorous mass of inflammatory tissue which constitutes the GVHR (8). The ratio Ki/Kc can be shown to depend upon the dose and type of parental cells inoculated (9), and provides a quantitative measure of the intensity of the 7th day GVHR.…”

“…Fifty million cells in 0.1 cc were injected under the capsule of the left kidney of an appropriate F1 as described previously (8). The hosts were sacrificed on the desired day and both kidneys and spleen removed.…”

Histocompatibility Antigens in the Rat: The As2 Strain in Relation to the As, Bs and Hs Strains

“…The technique was that describetl by Elkins (1964) except that a 26-gauge needle was used in preference to a 30-gauge needle. All VI hybrid recipients weie 8 weeks old and eaeb group comprised approx, equal nimibers of males aud females.…”

“…1). The following gradinR system, which is a slight motliKcution oi that used by Elkins (1964). has beon used for purposes of tabulation (Table 4) (ira<lf 0: Non-invasivf lesions of minimal severity in which lymphoid celk were infrequent or absent.…”