Lymphocyte Transformation Induced by Autologous Cells: Stimulation by Cultured Lymphoblast Lines

Weksler, Marc E.; Birnbaum, Gary

doi:10.1172/jci107139

Cited by 29 publications

(22 citation statements)

References 31 publications

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“…This phenomenon has been studied primarily in man (14)(15)(16)(17)(18)(19)(20) and to a lesser extent in mice (21)(22)(23). We have documented four new features of the mouse SMLR: (a) the DC is a uniquely potent stimulator cell; (b) DC-dependent T cell proliferation occurs in all cultures of mouse spleen and lymph node; (c) DC and responding T cells efficiently associate with one another in cell aggregates; and (d) neither T cell responsiveness nor DC stimulatory capacity are modified by immunization with tuberculin Ag.…”

Section: Discussionmentioning

confidence: 99%

“…This was based on the findings that B lymphocyte lines (14), E rosettedepleted leukocytes (15), and anti-Ig-selected leukocytes (20) functioned as stimulators. However, there is evidence that B cells do not represent the major stimulators in primary leukocyte populations (17,20). DC have yet to be identified in man, so their contribution has not been analyzed directly.…”

Section: Discussionmentioning

confidence: 99%

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Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction.

Nussenzweig¹,

Steinman²

1980

The Journal of Experimental Medicine

291

132

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We have studied the proliferative response of unprimed T cells to syngeneic dendritic cells (DC) (syngeneic mixed leukocyte reaction [SMLR]) in cultures of mouse spleen and lymph node. T cells purified by passage over nylon wool contain few DC and exhibits little proliferative activity during several days of culture. Addition of small numbers of purified syngeneic DC induces substantial, dose-dependent, T cell-proliferative responses that peak at day 4-5. B cells purified on anti-Ig-coated plates do not respond to DC at all doses tested. DC culture medium does not induce proliferation, and coculture of DC and T cells is required. Purified mouse B and T lymphocytes stimulate SMLR weakly if at all. Likewise, peritoneal and spleen macrophages are weak or inactive. Therefore, DC are potent and possibly unique primary cells for stimulating the SMLR in mice. sIg- spleen and lymph node cells show extensive background proliferative responses in vitro, and fail to respond to small numbers of purified DC. If the sIg- cells are treated with anti-Ia and complement, or passed over nylon wool, DC are removed and proliferative activity falls. Proliferative activity is restored by adding back DC at levels similar to those present in sIg- cells (1-2%). Thus, DC-dependent, T cell proliferation probably occurs in all spleen and lymph node cultures. As expected from previous work (6), DC are also potent inducers of allogeneic MLR. On a per DC basis, the syngeneic response is 10 times weaker than the allogeneic MLR, and it is not accompanied by the development of cytotoxic lymphocytes. The magnitude of the SMLR was not altered by antigen priming, and DC maintained in isologous rather than fetal calf serum were active stimulators. Therefore, syngeneic stimulation appears to be an intrinsic property of DC, and modification by exogenous agents does not seem to be required. Coculture of DC and T cells results in the development of cell clusters that can be isolated and characterized directly. The clusters account for 10-20% of the viable cells in the culture, but contain greater than 80% of the responding T cells and stimulating DC by morphologic and surface-marker criteria. The efficient physical association of DC and responding T cells implies specific cell-cell recognition. We conclude that the SMLR reflects the ability of T cells, or some subpopulation of T cells, to interact with and proliferate in response to small numbers of DC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction.

Nussenzweig¹,

Steinman²

1980

The Journal of Experimental Medicine

291

132

View full text Add to dashboard Cite

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“…It has been demonstrated that the AMLR provides a proliferative stimulus for the generation of cytotoxic T cells (11,30) and represents a defense mechanism against neoplastic transformation (12). Although the actual biological significance of the phenomenon is unclear, it may be important in host resistance against autologous tumor cells.…”

Section: Resultsmentioning

confidence: 99%

“…Although the biologic significance of this phenomenon is not yet clarified, the reaction can be demonstrated reproducibly in normal individuals and exhibits immunologic memory and specificity (11). The AMLR has been demonstrated to represent a natural defense mechanism against neoplastic transformation (12), to provide a proliferative stimulus for the generation of cytotoxic lymphocytes (11), and to regulate various immunologic functions such as production of antibody by B cells (13) and T cell response to mitogens and antigens (14,15). Although there is general agreement that the responding population in the AMLR is T cells, the nature of the stimulator cells has been reported variously as B cells (10), null cells (16), and monocytes (17).…”

Section: Introductionmentioning

confidence: 99%

Autologous mixed lymphocyte reaction in the peripheral blood and pleural effusions of cancer patients.

Uchida¹,

Micksche²

1982

J. Clin. Invest.

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“…The products of such immune responses, both antibodies and sensitized lymphocytes, seem capable of damaging tumour cells in defined experimental conditions (Hellstrom et al, 1971;Scornik & Klein, 1978). However, the significance of such responses to host resistance to tumour growth in vivo is still unclear, in view of the potential of immune reactants to enhance tumour growth (Prehn, 1972;Shearer et al, 1973) and recent observations suggesting immunological recognition of autologous non-malignant cells (Perlmann et al, 1977;Weksler et al, 1978).…”

mentioning

confidence: 99%

Immunoglobulins associated with human tumours in vivo: igg concentrations in eluates of colonic carcinomas

MacSween¹,

Eastwood²

1980

Br J Cancer

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Summary.-The concentrations of IgG in acidic and 3MKCl eluates of resected colonic carcinomas and adjacent normal tissue were determined by radioimmunoassay. The mean concentration of IgG was significantly higher in both acidic and KCI eluates of primary Dukes Stage C tumours than Dukes Stage A tumours. These results provide direct evidence for increased fixation of IgG in vivo by human colonic cancers which had metastasized. Our results also raise the possibility that IgG is more tightly bound to the Stage C tumours. It is likely that this tumour-associated Ig represents antibody to tumour antigens or antigen-antibody complexes, bound to Fc receptors in the tumour.

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Lymphocyte Transformation Induced by Autologous Cells: Stimulation by Cultured Lymphoblast Lines

Cited by 29 publications

References 31 publications

Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction.

Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction.

Autologous mixed lymphocyte reaction in the peripheral blood and pleural effusions of cancer patients.

Immunoglobulins associated with human tumours in vivo: igg concentrations in eluates of colonic carcinomas

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