Quantitative variation in la antigen expression plays a central role in immune regulation

Janeway, Charles A.; Bottomly, Kim; Babich, John F.; Conrad, Patricia J.; Conzen, Suzanne D.; Jones, Barry; Kaye, Jonathan; Katz, Michael E.; McVay, Laila D.; Murphy, Donal B.; Tite, J P

doi:10.1016/0167-5699(84)90043-4

Cited by 277 publications

(81 citation statements)

References 63 publications

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“…The inhibitory effects in vitro were obtained using levels of EPA and DHA which are achievable in blood plasma with relatively low supplementation with fish oil capsules (3 g/day) [15]. As Janeway and colleagues emphasized [6] …”

Section: Discussionmentioning

confidence: 99%

“…A prerequisite for this antigen-presenting cell (APC) function is the expression of MHC (which is known as the human leucocyte antigen (HLA) system in man) class II antigens, such as HLA-DR, HLA-DP and HLA-DQ [4]. It has been shown that the T cell proliferative response to antigen is proportional to the number of MHC class II molecules on the surface of APC [5], and that the percentage of MHC class II-positive cells and the density of these molecules on the cell surface can alter the degree of immune responsiveness of an individual [6].…”

Section: Introductionmentioning

confidence: 99%

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N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro

Hughes

Pinder

1997

Clinical and Experimental Immunology

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SUMMARYN-3 polyunsaturated fatty acid (PUFA)-rich diets are associated with suppression of cell-mediated immune responses, but the mechanisms are unclear. Specific immune responses are initiated by antigenpresenting cells (APC). We have previously shown in vitro that the n-3 PUFA, eicosapentaenoic acid (EPA), inhibits the expression of HLA-DR, an MHC class II molecule required for normal APC function on human blood monocytes. In contrast, docosahexaenoic acid (DHA) enhanced the expression of this molecule on unstimulated monocytes, but both n-3 PUFA suppressed its expression on interferongamma (IFN-g)-activated monocytes. In the present study we show that when EPA and DHA were combined at the same ratio as is commonly found in fish oil supplement capsules (3:2) there was no significant effect in vitro on the expression of HLA-DR on unstimulated monocytes, but the expression on IFN-g-activated monocytes remained significantly inhibited. In the same in vitro system a significant reduction in the ability of IFN-g-activated monocytes to present tetanus toxoid antigen to autologous lymphocytes was observed following culture with the combined n-3 PUFA. These findings support previous animal studies which suggest that n-3 PUFA can inhibit the antigen-presenting function of mononuclear phagocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro

Hughes

Pinder

1997

Clinical and Experimental Immunology

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“…Other molecules including cytokines and the cell surface adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and leukocyte-function-associated antigen-3 (LFA-3) also interact during antigen presentation to T cells. Immune responsiveness has been shown to be proportional to both the percentage of MHC class II positive monocytes and also to the density of these molecules on the cell surface (Janeway et al, 1984). Therefore, measures that can increase the expression of these molecules may enhance the immune response.…”

Section: Cd3mentioning

confidence: 99%

Low-dose supplementation with lycopene or β-carotene does not enhance cell-mediated immunity in healthy free-living elderly humans

et al. 2001

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Objective: To assess the effects of supplementation with the carotenoids, b-carotene or lycopene, at levels achievable within a diet rich in fruit and vegetables, on immune function in a group of free-living healthy elderly. Design: A double-blind randomized placebo-controlled trial. T cell subsets and the expression of functionally associated cell surface molecules, quanti®ed by¯ow cytometry, and lectin-stimulated lymphocyte proliferation, were compared before and following the treatment period. Subjects: Fifty-eight subjects aged over 65 y were recruited; 52 were included in the ®nal analysis. Interventions: Participants received one placebo, one lycopene (13.3 mg) or one b-carotene (8.2 mg) capsule daily for 12 weeks. Results: No signi®cant differences were observed in any of the parameters examined following either lycopene or b-carotene supplementation. Conclusions: In well-nourished, free-living, healthy elderly individuals, supplementation with relatively low levels of b-carotene or lycopene is not associated with either a bene®cial or detrimental effects on several aspects of cell-mediated immunity. Sponsorship: Financial support was provided by the Commission of the European Communities, speci®c programme AIR2 CT93-0888 DGXII SSMA,`Increased fruit and vegetable consumption within the EC: potential health bene®ts', co-ordinated by Professor S Southon, Institute of Food Research, Norwich, UK.

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“…Variability in the expression of these products is known to be capable of altering the degree of immune responsiveness of an individual to specific antigens such as tetanus toxoid [7]; and. in this study, we have also shown that pre-incubation of monocytes with cholesterol can significantly increase their capacity to present this antigen to autologous lymphocytes in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…macrophages and dendritic cells: and their expression can be induced ona number of other cell typres by the lymphokinc interferon-gamma (IFN-y) [5.6]. The percentage of MHC class ll-positivc monocytes and the density of these molecules on ihc cell surface can alter the degree of immune responsiveness of an individual (7], It has been proposed Ihat the increases in BAL lymphocyte numbers in patients wilh granulomatous lung diseases may be related to increased expression of HLA-D region antigens on Iheir aiveolar macrophages. Evidence in support of this suggestion was reported by Campbell et al [8], who observed that iilveoiar macrophages in BAL samples from patients with the granulomatous iung disease puimonary sarcoidosis show a significantly increased expression of HLA-DR compared with those from healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

Hughes¹,

Townsend²,

Haslam³

1992

Clinical and Experimental Immunology

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SUMMARYExtrinsic allergic alveolitis (EAA) (synonym: hypcrsensilivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocylic infiltrates in the pulmonary interstitial tissues. We have previously reported thai the numbers of lymphocytes in bronchoalveoiar iavage (BAL) samples in this disease correlate wilh leveis ofcholesierol and neutral lipid-ladcn 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which areknovtn lobe essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesteroi is capable of enhancing the antigenpresenting function of mononuciear phagocytes by moduiating the expression of HLA-D region products. Ineubation of purified monocytes from heaithy volunteers with cholesterol in serum-free medium induced a significant increase in bolh ihe percentages of monocyles expressing HLA-DQ (P< 002) and in Ihe intensity of expression of the three HLA-D sub-region products, HLA-DQ,-DP and -DR {P<0Q2. <001, <005, respeetiveiy). The choieslerol pre-incubated monocytes also exhibited enhanced antigen-presenting function (/'<005), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augmeni aniigen presentation by modulating the expression of HLA-D region products on anligen-preseniing cells. Apart from EAA. this observation may also have relevance lo inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.

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Quantitative variation in la antigen expression plays a central role in immune regulation

Cited by 277 publications

References 63 publications

N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro

N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro

Low-dose supplementation with lycopene or β-carotene does not enhance cell-mediated immunity in healthy free-living elderly humans

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

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