Recognition of Hapten-Modified Cells In Vitro by Human T Lymphocytes

Seldin, Michael F.; Rich, Robert R.; Abramson, Stuart L.

doi:10.1172/jci109563

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…of Vande Stouwe et al (13) that non-T cells are required for CTL development in response to heat-killed stimulators in man, and the studies of Seldin et al (14) in the TNP system appear analogous to the data in this paper.…”

Section: Discussionsupporting

confidence: 80%

Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes.

Nussenzweig¹,

Steinman²,

Gutchinov³

et al. 1980

The Journal of Experimental Medicine

233

114

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This study establishes that dendritic cells (DC) are the critical accessory cells for the development of anti-trinitrophenol (TNP) cytotoxic T lymphocytes (CTL) in vitro. We developed a model in which nylon wool-nonadherent spleen cells were used both as the responding and stimulating cells, the latter having been TNP-modified and x-irradiated. Thy-1-bearing CTL developed in C57BL/6, B6D2F1, and CBA mice only when small numbers of DC were added. Maximal responses in 5-d cultures were achieved with 0.5-1 DC/100 responding T cells. The DC did not have to be TNP modified directly. Anti-Ia and complement inactivated accessory cells, whereas similar treatment of the responders had no effect. DC exposed to ultraviolet radiation were ineffective, but x-irradiated DC were fully active. Culture media from DC, or from DC-nylon wool-passed spleen T cell cocultures that contained abundant CTL, would not substitute for viable DC. Enriched preparations of macrophages (M phi) were obtained from blood, peritoneal cavity, and spleens of BCG-immune and unprimed mice. M phi added at doses of 0.2-4% were weak or inactive as accessory cells. The level of Ia antigens on test M phi populations was quantitated and visualized by binding of a radioiodinated monoclonal anti-I-Ab,d antibody, clone B-21. M phi that bore substantial amounts of Ia from all organs were weak accessory cells. Addition of M phi to DC-T cell cocultures produced inhibitory effects, usually at a dose of 2% M phi. In contrast, 0.5% Ia-bearing M phi from BCG-immune boosted mice inhibited > 80% of the DC-mediated CTL response. Addition of indomethacin reversed M phi inhibition, and 10(-9) M prostaglandin E2 in turn blocked the indomethacin effect. Indomethacin also restored a low level of accessory cell function in immune-boosted adherent peritoneal cells, but not in preparations of monocytes and spleen M phi. Small numbers of DC were identified in preparations of immune-boosted peritoneal cells and may have accounted for the observed accessory activity. We conclude that the development of anti-TNP CTL is an immune response in which (a) DC are the critical accessory cells; (b) Ia-bearing M phi are weak or inactive; and (c) M phi can inhibit DC-mediated response by an indomethacin-sensitive mechanism.

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Section: Discussionsupporting

confidence: 80%

Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes.

Nussenzweig¹,

Steinman²,

Gutchinov³

et al. 1980

The Journal of Experimental Medicine

233

114

View full text Add to dashboard Cite

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“…Moreover, adding back graded numbers of macrophages did not increase the response; in fact, macrophages were somewhat suppressive at higher doses. Dose-response data in our previous studies (16,18) demonstrated that the hierarchy of proliferative responses induced by subpopulations was similar at several cell concentrations (from 1 × 104 to 2 × 105 per well). Non-T cells were always more effective stimulators than PBMC or monocytes.…”

Section: Ia-bearing Lymphoid Subpopulations Can Stimulate Primed Cellmentioning

confidence: 75%

“…Procedures. PBMC were separated as previously described into macrophage, non-T lymphocyte, and T lymphocyte subpopulations (18). T cells were >92% E-rosette +, <2% surface immunoglobulin +, <0.3% esterase +, and <5% Ia +.…”

Section: Cell Fractionationmentioning

confidence: 99%

Antigen presentation to human T lymphocytes. I. Different requirements for stimulation by hapten-modified cells vs. cell sonicates.

Abramson¹,

Puck²,

Rich³

1981

The Journal of Experimental Medicine

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We have investigated the cellular and antigenic requirements for incubation of secondary proliferative responses by human T lymphocytes. Two distinct properties of antigen-presenting peripheral blood mononuclear cells were studied: (a) the ability for appropriate cell surface constituents to construct an immunogenic moiety, and (b) the ability to present similar antigenic determinants when they are not covalently bound. Only Ia+ hapten-modified cells were effective stimulators. In contrast, both Ia+ and Ia- cell sonicates could stimulate secondary proliferative responses, but only in the presence of an accessory cell. This accessory cell was present in Ia+ macrophage, but not in Ia+ non-T lymphocyte, preparations. In contrast, macrophages or soluble factors produced by macrophages were not required for primed T cells to undergo hapten-specific proliferation in response to hapten-modified Ia+ stimulator cells. Thus, although all Ia+ cells tested can stimulate primed cells to proliferate, not all Ia+ cells can function as accessory cells for responses to sonicates. This may reflect the unique ability of a subpopulation(s) of Ia+ cells to bind or process sonicates or soluble antigens for appropriate recognition by primed T cells.

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