The Generation of Specific Cytotoxic Responses by Human Lymphocytes Requires Antigen and Activities Provided by a Lymphokine Supernatant‐

Warren, Hilary S.

doi:10.1111/j.1365-3083.1981.tb00185.x

Cited by 11 publications

(15 citation statements)

References 18 publications

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“…Procedures for the isolation of peripheral blood mononuclear cells (PBMC) and the subsequent isolation of resting lymphocytes (R-Ly) were essentially those described previously (12). In brief, PBMC were cultured in IL-2-CM for 3 days toensure full activation of all IL-2-responsive cells.…”

Section: Isolation Of Resting Lymphocytesmentioning

confidence: 99%

“…Cytotoxic activity is expressed as Cytotoxic Units (CU) (9,12). One CU = -Yo In (1-y), where Yo is the number of target cells, and y is the proportion of target cells lysed.…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

“…We define resting lymphocytes (R-Ly) as a subpopulation of PBMC which do not respond to IL-2-CM in short term (3 days) culture, and they are isolated according to this criterion (9,12). R-Ly are predominantly TCR2 cells (CD2+: 95±1; CD3+: 92±4; WT31+: 89±5; « = 8).…”

Section: Definition Of Resting Lymphocytes (R-ly)mentioning

confidence: 99%

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Resting (IL‐2 non‐responsive) precursors of human T cell receptor γδ‐positive cells (TCR1 cells) are activated by a two signal process

Warren¹

1989

Immunol Cell Biol

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Summary Precursors of T cells expressing the yS-T cell receptor (TCR 1 cells) have been identified in a resting (IL-2 non-responsive) subpopulation of human peripheral blood mononuclear cells (PBMC). Activation ofthe TCRl precursor cells into proliferating and cytotoxic cells requires two signals, viz. IL-2 and either activated T cells (autologous or allogeneic) or malignant melanoma cells (MM-170). The activation process is inhibited by 0-1 |i.g/ml cyclosporine. CD3 expression on TCRl precursor cells was low, since the precursor cells were not always adequately depleted by OKT3 plus complement. Natural killer cells were generated from the same resting subpopulation of PBMC and by the same set of activation stimuli as were the TCRl cells, suggesting a common pathway for activation of both cell types.

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Section: Isolation Of Resting Lymphocytesmentioning

confidence: 99%

“…Cytotoxic activity is expressed as Cytotoxic Units (CU) (9,12). One CU = -Yo In (1-y), where Yo is the number of target cells, and y is the proportion of target cells lysed.…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

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Resting (IL‐2 non‐responsive) precursors of human T cell receptor γδ‐positive cells (TCR1 cells) are activated by a two signal process

Warren¹

1989

Immunol Cell Biol

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“…Thus, LK is required for the generation of cytotoxic responses to alloantigens (Talmage et al, 1977;Lafferty, Andrus and Prowse, 1980), tumour-associated antigens (Warren and Lafferty, 1979;Mills and Paetkau, 1980) and hapten-modified syngeneic cells (Wagner et al, 1980;Gillis and Watson, 1981). The in vitro generation of specific cytotoxic responses by human lymphocytes to xenogeneic cells is also dependent upon LK (Warren, 1981). In this paper data are presented showing that human LK is required for the generation of specific cytotoxic responses to an allogeneic malignant melanoma cell line, MM-170.…”

Section: Introductionmentioning

confidence: 99%

“…Balanced salt solutions and the tissue culture medium (TCM) used were as detailed previously (Warren, 1981).…”

Section: Mediamentioning

confidence: 99%

HUMAN ALLOGENEIC RESPONSES: LYMPHOKINE REQUIREMENT FOR THE IN VITRO GENERATION OF SPECIFIC CYTOTOXIC RESPONSES TO A MALIGNANT MELANOMA CELL LINE

Warren

Pembrey

Wildermuth

1982

Aust J Exp Biol Med

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Summary Requirements for the in vitro generation of specific cytotoxic responses by human T‐lymphocytes to an allogeneic malignant melanoma cell line (MM‐170) have been examined. The responder T‐lymphocytes used were isolated from peripheral blood and were essentially free of non‐specific cytotoxic effector cells and their precursors. MM‐170 alone was found to be an inadequate stimulator of cytotoxic responses. Stimulation did occur in cultures with both MM‐170 and an Interleukin‐2 containing human lymphokine supernatant. The cytotoxic effector cells generated were specific for MM‐170 when the MM‐170 cells used for stimulation had been metabolically inactivated by glutaraldehyde treatment.

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Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2

Hersey

Bindon

Edwards

et al. 1981

Intl Journal of Cancer

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The influence of interleukin 2(IL2) on the cytotoxic activity of lymphocytes from patients with melanoma against autologous and a variety of allogeneic melanoma cells was studied. IL2 was produced from blood lymphocytes cultured for 24 h with phytohaemagglutinin (PHA) and purified by membrane chromatography to exclude PHA. Lymphocytes from 13 patients with melanoma at various clinical stages were cultured fro 6 days with IL2 (2 U/ml) and then tested for cytotoxic activity against autologous melanoma cells, three allogeneic melanoma and three non-melanoma cells. Autologous cytotoxicity was generated by culture with IL2 alone and was not increased by culture with both IL2 and autologous tumour cells. Marked increases in cytotoxic activity were also generated against the allogeneic target cells and were maximal against the NK-insensitive Chang target cells. Similar degrees of cytotoxicity were induced by IL2 stimulation of lymphocytes from melanoma patients, patients with nonmelanoma carcinoma and normal subjects against the allogeneic target cells. Cold target inhibition studies were carried out against IL2 induced autologous cytotoxicity in five patients. In four of five studies the autologous target cells inhibited more than the allogeneic target cells. There was no significant difference between the inhibition produced by allogeneic melanoma cells and that produced by non-melanoma cells. Similarly, in studies against allogeneic target cells, there was no significant difference in the inhibition produced by allogeneic melanoma compared to non-melanoma target cells. This applied irrespective of whether effector cells were from melanoma or non-melanoma subjects. These results suggest that lymphocytes from patients with melanoma are primed against autologous antigens in vivo and that provision of a second signal, IL2, in vitro can induce cytotoxicity against the autologous tumour. The cytotoxicity generated against the allogeneic target cells did not appear to have specificity to melanoma. Several results, such as the pattern of cytotoxicity against the target cells and change in cell surface markers on the lymphocytes during culture, suggested that cytotoxicity was mediated by activated T cells rather than by nature killer cells. These findings appear to have important implications both in the understanding of tumor host relationships and for the use of IL2 in therapy.

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The Generation of Specific Cytotoxic Responses by Human Lymphocytes Requires Antigen and Activities Provided by a Lymphokine Supernatant‐

Cited by 11 publications

References 18 publications

Resting (IL‐2 non‐responsive) precursors of human T cell receptor γδ‐positive cells (TCR1 cells) are activated by a two signal process

Resting (IL‐2 non‐responsive) precursors of human T cell receptor γδ‐positive cells (TCR1 cells) are activated by a two signal process

HUMAN ALLOGENEIC RESPONSES: LYMPHOKINE REQUIREMENT FOR THE IN VITRO GENERATION OF SPECIFIC CYTOTOXIC RESPONSES TO A MALIGNANT MELANOMA CELL LINE

Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2

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