Natural cytotoxicity in rats: Strain distribution and genetics

McNeilage, L J; Heslop, Barbara F.; Heyworth, M.R.; Gutman, George A.

doi:10.1016/0008-8749(82)90482-8

Cited by 15 publications

(22 citation statements)

References 17 publications

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“…Recipients of heat-killed syngeneic cells show a seven to eight-fold increase in kidney radioactivity 24 h after injection when compared with the recipients of viable cells, but at best a two-fold increase in the liver radioactivity (Heslop & Hardy 1971, unpublished observations). In the 13/95 allogeneic strain com-binadons reported by McNeilage et al (1982) as showing high NC, the mean kidney radioactivity at 24 h was 1.74 (SD 0.6) times that seen in syngeneic controls; the mean liver radioactivity on the other hand (I.Ol; SD 0.07) was not significantly different from that of syngeneic controls.…”

Section: Criteria Of Death Of Intravenously Injected *'Cr-labelled Lymentioning

confidence: 72%

“…Likewise, radio-labelled lymphocytes successfully colonize the lymph nodes of both splenectomised allogeneic hosts (McNeilage .fe Heslop 1980) and immature allogeneic hosts ( Figure I). Of 95 allogeneic strain combinations examined by McNeilage et al (1982), the extent to which radio-labelled lymphocytes accumulated in the lymph nodes of allogeneic hosts could not be correlated exactly with the extent to which donor and host differed at the MHC. Of the 13 strain combinations exhibiting high NC (i.e.…”

Section: Characteristics Of Natural Cytotoxicity In Ratsmentioning

confidence: 91%

“…Radioactivity has been routinely measured 24 h after injection because at this time (i) the lymph node radioactivity in syngeneic animals is at its peak, and (ii) syngeneic-atlogeneic differences are at or near their peak with respect to the radioactivity recovered from lymph nodes, liver, blood, kidneys and urine, and also for the total radioactivity recovered from the organ sampled (McNeilage & Heslop 1980). A given host strain exhibits NC against a specified allogeneic donor strain when the lymph node radioactivity at 24 h is significantly lower and the kidney and urine radioactivity is significantly higher than that recorded in syngeneic recipients of the same cell suspension (McNeilage et al 1982). Allogeneic hosts exhibiting NC may also show several other differences from syngeneic controls, i.e.…”

Section: Characteristics Of Natural Cytotoxicity In Ratsmentioning

confidence: 97%

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Natural Cytotoxicity: Early Killing of Allogeneic Lymphocytes in Rats

Heslop

Neilage

1983

Immunological Reviews

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In many strain combinations among inbred rats, intravenously injected 51Cr-labelled lymphocytes are destroyed in substantial numbers by unsensitized allogeneic hosts. Destruction of cells (referred to as natural cytotoxicity (NC)) occurs within a few hours of injection, and is characterised by a decreased accumulation of radioactivity in the lymph nodes and increased renal excretion of label by allogeneic hosts, as compared with the distribution of label in syngeneic recipients of the same cell suspension. An intact spleen is necessary for killing. The level of NC expressed is consistent for a given donor-host combination. Using arbitrary criteria to compare the levels of NC expressed by different donor-host combinations among inbred rats, 13 of 95 strain combinations have been shown to express high NC, 63 intermediate NC and 19 low NC. The level of NC expressed cannot be correlated with the extent to which donor and host differ in respect of known MHC genes. Segregation analysis has shown high NC to be controlled by at least 2 independently segregating genes, one of which is MHC-linked. It is possible to weaken or abrogate NC by the neonatal injection of bone-marrow cells from the donor strain, and to reverse this reduced reactivity by the injection of host strain lymphocytes. The substitution of either the donor (P1) or the host (P2) by the P1 X P2)F1 hybrid reduces or eliminates NC in strain combinations normally expressing high NC. It is currently uncertain whether NC can be augmented. In the single strain combination in which maturation has been studied, NC becomes evident during the 4th week of life and attains adult levels during the 6th-7th weeks. NC is at least partially radio-sensitive. Two groups of reactivities appear to be related to NC: (i) those which have been identified in the context of aberrant lymphocyte homing, and for which allogeneic lymphocytes are the targets; (ii) the group of natural resistance systems which includes NK cells, and whose reactivity is directed against a variety of other target cells.

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Section: Criteria Of Death Of Intravenously Injected *'Cr-labelled Lymentioning

confidence: 72%

Section: Characteristics Of Natural Cytotoxicity In Ratsmentioning

confidence: 91%

Section: Characteristics Of Natural Cytotoxicity In Ratsmentioning

confidence: 97%

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Natural Cytotoxicity: Early Killing of Allogeneic Lymphocytes in Rats

Heslop

Neilage

1983

Immunological Reviews

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“…into naïve normal recipients, were sometimes eliminated as soon as they had left the blood stream (15, 16). MHC genes were clearly involved (17) but other factors also played a role, since this rapid elimination was also dependent on genes outside the MHC complex (15, 18, 19). The elimination took place in the lymphoid tissue (15, 16) more specifically within the T cell areas of lymph nodes and spleen (20).…”

Section: Rat Nk Cell Alloreactivity: a Model Organism For Studying Somentioning

confidence: 99%

The Early Days of NK Cells: An Example of How a Phenomenon Led to Detection of a Novel Immune Receptor System â€“ Lessons from a Rat Model

Rolstad

2014

Front. Immunol.

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In this review, I summarize some of the early research on NK cell biology and function that led to the discovery of a totally new receptor system for polymorphic MHC class I molecules. That NK cells both could recognize and kill tumor cells but also normal hematopoietic cells through expression of MHC class I molecules found a unifying explanation in the “missing self” hypothesis. This initiated a whole new area of leukocyte receptor research. The common underlying mechanism was that NK cells expressed receptors that were inhibited by recognition of unmodified “self” MHC-I molecules. This could explain both the killing of tumor cells with poor expression of MHC-I molecules and hybrid resistance, i.e., that F1 hybrid mice sometimes could reject parental bone marrow cells. However, a contrasting phenomenon termed allogeneic lymphocyte cytotoxicity in rats gave strong evidence that some of these receptors were activated rather than inhibited by recognition of polymorphic MHC-I. This was soon followed by molecular identification of both inhibitory and stimulatory Ly49 receptors in mice and rats and killer cell immunoglobulin-like receptors in humans that could be either inhibited or activated when recognizing their cognate MHC-I ligand. Since most of these receptors now have been molecularly characterized, their ligands and the intracellular pathways leading to activation or inhibition identified, we still lack a more complete understanding of how the repertoire of activating and inhibitory receptors is formed and how interactions between these receptors for MHC-I molecules on a single NK cell are integrated to generate a productive immune response. Although several NK receptor systems have been characterized that recognize MHC-I or MHC-like molecules, I here concentrate on the repertoires of NK receptors encoded by the natural killer cell gene complex and designed to recognize polymorphic MHC-I molecules in rodents, i.e., Ly49 (KLRA) receptors.

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“…Hypotheses about the biological functions of an NK-like allorecognition system responsible for the elimination of allogeneic cells within the lymphohematopoietic system must account for the following characteristics of ABC and ALC: 1) the rapid onset and no requirement for sensitization, but probably also no immunological memory~ 2) the strong linkage to MHC, although the target antigens are probably not the MHC class I or II antigens themselves, 3) that ALC can discriminate between target cell specificities from different MHC-incompatible strains, and that different receptor specificities are probably present on different effector cell populations, 4) the lack of association with any of the known rearranging receptor genes within the adaptive immune system, 5) the observation that an MHCincompatibility is a neccessary, but not sufficient requirement for ALC, since most donor-recipient combinations differing with respect to MHC antigens display no ALC (McNeilage et al 1982), and 6) biological features of the effector cells showing fundamental differences from cells of the adaptive immune system in that they are relatively short-lived cells and do not recirculate between blood and lymph as do T and B cells.…”

Section: Putative Biological Roles Of Alc and Abcmentioning

confidence: 99%

Non-adaptive cellular immune responses as studied in euthymic and athymic nude rats

Rolstad

Fossum

1990

Anat Embryol

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The athymic nude (rnu) rat lacks a functional thymus and normal alloreactive T cells. These animals, therefore, have been widely used as tools for studying thymus-independent immune responses. The absence of functional T cells would, to most investigators, indicate that these rats have a defective cellular immune defence. However, although rnu rats accept organ allografts infinitely, they are nevertheless capable of rejecting allografts consisting of lymphocytes or bone marrow cells with increased vigour, and this via antibody-independent mechanisms. These rejection phenomena have operationally been termed allogeneic lymphocyte cytotoxicity (ALC) and allogeneic bone marrow cell cytotoxicity (ABC). Unlike organ allograft immunity this kind of rejection requires no presensitization of the recipient and is surprisingly rapid: it commences within a few hours of i.v. injection of the allogeneic cells and is usually complete by 24 h. Moreover, products coded for by genes within, or closely linked to the major histocompatibility complex (MHC), are clearly involved in the interaction between effector and target cells, as grafted cells from MHC-congenic rat strains are vigorously rejected. In contrast to the defective T cell immune responses in athymic nude rats, the natural killer (NK) cell function is not impaired, and it has been suggested that the spontaneous rejection of MHC-incompatible lymphohematopoietic cells is in fact mediated by NK cells. If the MHC antigens themselves serve as targets in this kind of allorejection, this hypothesis is in apparent contrast with the prevailing view that recognition by NK cells is not guided by, or directed against, MHC-antigens on the target cell surface. Aging athymic nude mice and rats generate cells that rearrange and express T cell receptor (TCR) genes, and this has raised the possibility that T cells or T-like cells in athymic nude animals are responsible for ALC and ABC. This possibility urged the device of an in vitro test system for identification and further characterization of the effector cells in these rejection phenomena. Under appropriate conditions, cells from the rnu rat spleen or liver with natural killer function, i.e. the ability to lyse certain kinds of tumor cells in vitro, are also spontaneously cytotoxic for allogeneic small lymphocytes and bone marrow cells in vitro. Furthermore, these cells can be grown in vitro in the presence of interleukin 2 (IL-2) to generate populations of lymphokine-activated killer (LAK) cells, and these cells have the same spectrum of alloreactivity in ALC and ABC as the native NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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Natural cytotoxicity in rats: Strain distribution and genetics

Cited by 15 publications

References 17 publications

Natural Cytotoxicity: Early Killing of Allogeneic Lymphocytes in Rats

Natural Cytotoxicity: Early Killing of Allogeneic Lymphocytes in Rats

The Early Days of NK Cells: An Example of How a Phenomenon Led to Detection of a Novel Immune Receptor System â€“ Lessons from a Rat Model

Non-adaptive cellular immune responses as studied in euthymic and athymic nude rats

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