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The effects of normal pregnancy on peripheral blood lymphocytes were investigated. The frequencies of thymus-derived and bone-marrow-derived lymphocytes in maternal peripheral blood does not vary significantly throughout pregnancy. This observation implies qualitative rather than quantitative alterations in lymphocyte functions to explain the reduced cell-mediated immune responses seen during pregnancy. [ABSTRACT FROM AUTHOR]

A phenomenon we have termed spontaneous lymphocyte-mediated cytotoxicity (SLMC) by non-thymus-derived lymphocytes from normal donors has been described. The phenomenon can be demonstrated using human and xenogeneic (mouse) cell lines as the target cell in a microplate 51Cr release assay which is simple and reproducible. In this paper, SLMC against xenogeneic targets has been evaluated as a potential marker of lymphocytotoxic function with respect to; (a) the nature of the target cell; (b) the variability of the cytotoxic function of lymphocytes from different donors, and from the same donor tested on different days: (c) the nature of the effector cell. Using buoyant density centrifugation of iron plus magnet-purified lymphocytes forming rosettes with sheep red blood cells (SRBC) (T cells) or SRBC--rabbit 19S anti-SRBC--mouse complement (complement receptor lymphocytes), it has been demonstrated that the cytotoxic activity lies in the non-T-lymphocyte fraction, and is probably caused by the complement receptor-bearing lymphocyte. The potential usefulness of this phenomenon as a functional marker of non-T-lymphocyte cytotoxic ability, and for the assessment of serological factors which may affect this cytotoxicity, has been discussed. [ABSTRACT FROM AUTHOR]

Lymphocytes from six Chediak Higashi (CH) patients were markedly depressed in their ability to lyse tumour cell targets in both 51Cr release and single cell cytotoxicity assays. The frequency of lymphocytes bearing the OKM1 marker and the frequency of T3+, T4+, T8+, la-, Mol+, Mo2+ and BI+ cells was normal among sheep erythrocyte rosetting (E+ ) and non-resetting (E-) peripheral blood leucocytes analysed by flow cytofluorography. Cells expressing the NK shared markers. OKMI mac-1, FcR, and the characteristic large granular lymphocyte (LGL) morphology of NK cells were also present in normal numbers in the highly enriched NK fraction separated on Percoll density gradients. This fraction did not contain detectable numbers of cells expressing the Mo2 marker of human monocytes. Therefore most of the cells stained by monoclonal OKMI and mac-1 in this fraction are likely NK cells, rather than monocytes. and we conclude that the size of the NK pool in CH patients is probably normal. The capacity of CH lymphocytes to recognize anti bind to tumour cells was also normal as was the subsequent burst at oxygen intermediates produced by the NK cells in a chemiluminenscence assay We have shown elsewhere that O2 generation is directly involved in activating subsequent steps in the NK cytolytic pathway. These results suggest that NK cells in CH patients are present in normal frequency but are blocked at some post-recognition, post-activation step in the cytolytic pathway subsequent to the burst of oxygen intermediates but preceding the lethal hit. [ABSTRACT FROM AUTHOR]

Class I MHC-expressing (Ia-) immunogenic (imm+) variants, which elicit a strong syngeneic host immune rejection response, can be isolated following 5-azacytidine treatment from the MHC-negative non-immunogenic (imm-) murine carcinoma cell line SP1 (10.1 subclone). In the present study, we have shown that CD4-depleted CD8+ T cells are both necessary and sufficient for the rejection process. Treatment of semi-syngeneic B6 × CRA F1 mice with anti-NK 1.1 antibodies had no effect on the rejection of immunogenic variants, although the splenic NK (natural killer) activity of recipients was fully abrogated. Thus NK 1.1+ effectors, which include most NK and LAK (lymphokine activated killer) cells, are most likely not involved in the rejection process. This finding was supported by a complete lack of NK susceptibility of SPI cells in vitro, although variable killing by LAK and poly-I: C-induced killer cells was observed. To assess the role of NK 1.1- LAK and other non-T killers (e.g. cytolytic macrophages) in vivo, we determined the specificity of the rejection process. We examined the ability of immune animals to reject a mixture of non-immunogenic parent tumour cells (or cells of an unrelated syngeneic tumour) and of the variant tumour cells used for the initial immunization, Growth of the parent tumour cells was unaffected while the same animals rejected the immunogenic tumour cells. Our findings support a primary role of tumour-specific CD8+ T cells in the rejection of imm+ variants with no detectable involvement of non-specific effector cells in the tumour destruction process. [ABSTRACT FROM AUTHOR]

The surface characteristics of the mouse spleen cells mediating antibody-dependent cytotoxicity (ADCC) against antigen-coated chicken erythrocytes have been studied by several different column fractionation methods. The major effector cells in this system were shown to be surface-adherent and could be depleted from spleen cells by passage through glass-bead ovalbumin/anti-OA immune complex columns (Fc receptor-binding), glass-bead immunoglobulin/anti-mouse Ig columns (Fc receptor- and surface immunoglobulin-binding), and glass-bead mouse Ig/rabbit (Fab')2-anti-mouse Ig or Sephadex G-200/rabbit anti-mouse Ig columns (surface immunoglobulin-binding). The concentration of EDTA in the medium used to fractionate the cells played a significant role in determining whether surface immunoglobulin could be demonstrated on the ADCC effector cells. From these results, the conclusion was drawn that ADCC on the part of mouse spleen cells could be mediated by surface-adherent, Fc receptor-positive cells bearing surface immonoglobulin of unknown origin. The possibility that ADCC can be mediated by a heterogenous population of cells in the mouse spleen is discussed. [ABSTRACT FROM AUTHOR]

Spontaneous natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of blood lymphocytes against five human tumour cell lines (K562, Molt-4, HL-60, Chang, Daudi) and three mouse tumour lines (YAC, P815, RBL-5) were ten- to 100-fold lower than normal in six patients with Chediak-Higashi (CH) disease. NK and ADCC were defective at 4 hr, and less so at 18 hr. The NK activity in normals and CH patients was mediated in part by FcR+, E- effector cells. ADCC against human erythrocytes was normal in CH patients, as were lectin-dependent cytolysis and mixed lymphocyte proliferative responses. Phagocytosis of antibody-coated ox erythrocytes was normal in CH patients as well, These observations confirm that the CH syndrome is associated with a profound and selective defect in NK and ADCC activity against tumour cells, whereas other mononuclear cell-mediated functions are normal. [ABSTRACT FROM AUTHOR]

Mice mated with H-2 incompatible males were shown to have an increased frequency of specific allocluster forming spleen cells to paternal strain erythrocytes. The time course of the response was similar to that expected following a skin allograft. The graft-versus-host responsiveness of the maternal lymphocytes was generally elevated in the post-partum period in matings with males incompatible at either the H2 locus or non-H2 loci. The implications of these responses with respect to their different lymphocyte mediators and possible interactions are discussed with the view that a B-cell mediated immune response to paternal antigens may be contributory to foetal survival. [ABSTRACT FROM AUTHOR]

The experiments described in this paper extend the observations of previous work in vitro demonstrating a decrease in the frequency of antigenreactive units specific for horse RBC in spleen cells from mice primed with KLH. It was observed that the addition of lymphoid cells having T-cell function reconstituted the anti-HRBC response to normal values. Significant enhancement of the response beyond the normal values could be evoked using two dissimilar methods, (i) addition of allogeneic thymus cells, and (ii) restimulation in vitro with the priming antigen. The latter type enhancement was elicited by the addition of small doses of KLH to cultures of spleen cells from mice recently primed with KLH, including cultures otherwise demonstrating antigen-induced suppression. The stimulus required to enhance the response to HRBC in these cultures was specific for the priming antigen, KLH. These results are discussed in the light of current theories of 'antigenic competition' and specific heterologous enhancement. [ABSTRACT FROM AUTHOR]

The reconstitutive capacity of normal lymphoid cells versus cells obtained from mice immunized with keyhole limpet haemocyanin was studied in lethally irradiated syngeneic recipients using horse erythrocytes as the test antigen. Evidence was obtained for an immune deficiency in the inoculum from immune donors, which was interpreted as evidence in favour of a cellular mechanism to account for antigen-induced suppression ('antigenic competition'). The unexpected inhibition of reconstitution with excessive numbers of normal spleen cells was duplicated in experiments using thymus or thymus-derived cells. Experiments assessing the effect of cortisone-resistant thymus cells on the response of normal spleen cells, in vivo and in vitro, gave evidence that a relative surplus of such thymus cells possess a capability for suppressing antibody formation. Since helper function by T cells is now well documented, this work is further indicative of the broader view, namely immuno-regulation by T cells. [ABSTRACT FROM AUTHOR]