Development and persistence of cytolytic T lymphocytes in regressing or progressing moloney sarcomas

Gillespie, G. Yancey; Russell, Stephen W.

doi:10.1002/ijc.2910210116

Cited by 16 publications

(12 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results of the experiments described here and in earlier publications (Gillespie et al, 1977;Gillespie and Russell, 1978) allow 3 conclusions to be drawn about tumour-T-lymphocyte interrelationships in the Moloney system: (1) an in vivo control mechanism stops the production of cytolytic T lymphocytes in lymphnodes draining either regressing or progressing Moloney sarcomas; (2) after they have reached a non-cytolytic state, explantation of T lymphocytes from tumourdraining lymph nodes into culture releases them from whatever influence it is that prevents the production of killer cells in vivo, allowing a resurgence of cytolytic activity in vitro: and (3) cytolytic cells generated from non-cytolytic T lymphocytes in tumour-draining lymph nodes have powerful protective effects against tumour progression in vivo.…”

Section: Discussionsupporting

confidence: 63%

“…Cell lines were maintained and cells harvested from culture as previously described (Gillespie et al, 1977 (Russell et al, 1976a;Gillespie and Russell, 1978). Fe-receptor-bearing cells (mostly B lymphocytes and some macrophages) were depleted by incubation of LNC suspensions on monolayers of antibodysensitized sheep erythrocytes (Kedar et al, 1974 to each tube to slow cell metabolism, and the contents of each tube were deposited onto cellulose-acetate membranes (045 ,um pore size) by vacuum filtration.…”

Section: Methodsmentioning

confidence: 99%

“…This assay and the calculation of LU have been described previously (Gillespie et al, 1977;Gillespie and Russell, 1978) and allow direct comparison of the relative cytolytic activities of different LNC populations.…”

Section: Methodsmentioning

confidence: 99%

“…Because macrophages had previously been shown to inhibit the development of cytotoxicity in vitro (Gillespie and Russell, 1978), we examined the effect of removing the few M0 that were normally present in our LNC populations, along with other Fe-receptor-bearing types either before or after culture. LNC suspensions depleted of MO before culture mediated levels of tumour-specific killing (43 and 55 LU/106 T cells after 2 and 4 days, respectively) that were comparable to those of LNC (Russell and Cochrane, 1974).…”

Section: Effect Of Culture Conditions On Cytolytic Activitymentioning

confidence: 99%

“…We have additionally shown that T cells with lytic activity can be isolated directly from progressing Moloney sarcomas, but only during the early stages of tumour development (Gillespie et al, 1977). Thereafter, T lymphocytes recovered either from progressing sarcomas or from the lymph nodes draining these lesions lacked the ability to kill (Gillespie and Russell, 1978).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Resurgence of killing and in vivo protection mediated by lymphocytes cultured from lymph nodes draining Moloney sarcomas

Gillespie¹,

Hansen²,

Russell³

1978

Br J Cancer

View full text Add to dashboard Cite

Summary.-We have previously documented the development and subsequent disappearance of cytolytic activity mediated by lymphocytes from lymph nodes draining Moloney sarcomas destined either to regress or grow progressively. We now report that these tumour-draining lymphnode cells (LNC) that were no longer cytotoxic, spontaneously regenerated peak levels of killing after culture in vitro for 4 days in the absence of exogenous tumour antigen. Cytolytic activity, which was antigenically specific, was mediated by T lymphocytes. Resurgence of cytolytic activity in vitro was accompanied by proliferative changes (DNA synthesis, blast transformation, cell division) which peaked on the 3rd day of culture. Although normal, nonimmune LNC underwent quantitatively similar proliferative changes in culture, the killing that developed was weak and antigenically nonspecific. Transfer of cultured, tumourdraining LNC to immunologically compromised, syngeneic mice conferred complete protection from Moloney sarcoma progression. Adoptive transfer could be delayed for 6 days after tumour induction without loss of protection. These results suggest that there exists in Moloney sarcoma-bearing mice a mechanism that limits the differentiation of pre-killer cells into cytolytically active T lymphocytes, and that such inhibition is eliminated when LNC are explanted into culture.

show abstract

Section: Discussionsupporting

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Effect Of Culture Conditions On Cytolytic Activitymentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Resurgence of killing and in vivo protection mediated by lymphocytes cultured from lymph nodes draining Moloney sarcomas

Gillespie¹,

Hansen²,

Russell³

1978

Br J Cancer

View full text Add to dashboard Cite

show abstract

Characterization of lymphocyte subsets in spontaneous mouse mammary tumors and host lymphoid organs

Santer

Mastromarino

Lala

1980

Intl Journal of Cancer

View full text Add to dashboard Cite

The subsets of small lymphocytes (surface Igm-positive or B, Thy-I-positive or T and "double-negative" or null) appearing within spontaneous mammary tumors of C3H retired breeder female mice and in various lymphoid organs of the host at different stages of tumor development were characterized directly using a radioautographic method. Tumor-bearing mice showed early transient splenomegaly and progressive atrophy of the thymus. The proportion of T small lymphocytes increased with tumor age within the tumor and in the spleen, blood and thymus; then, except in the spleen, these proportions declined again by 8 weeks of tumor growth. The incidence of B small lymphocytes showed no change in the tumor or thymus; there was an increase in the blood after 3 weeks, and a small decrease in the spleen after 7 weeks. At all the sites examined, the proportion of null small lymphocytes declined from an initial high level observed in the elderly tumor-free control mice, and then recovered to control levels after 7 weeks. The absolute numbers of T and null cells in the spleen changed in parallel to their proportions, while splenic B-cell numbers increased at 1-3 weeks. In the thymus the absolute numbers of all subsets decreased, with a late recovery of null cell numbers. Age-matched control mice showed higher proportions of null cells in the spleen, blood and thymus, and lower proportions of T cells in the blood and spleen, than did young normal mice. This spontaneous tumor appears to be characterized by an increase in T cells, rather than in null cells, as observed for rapidly growing transplanted tumors. The null cell rise in the present case takes place before the clinical appearance of tumors. In both cases, however, tumor-infiltrating B cells exhibited low levels of surface Ig, possibly related to a low level of maturation. The functional significance of these findings remains to be determined.

show abstract

Enhancement or inhibition of tumor growth by interferon: Dependence on treatment protocol

Murasko

Fresa

Mark

1983

Intl Journal of Cancer

View full text Add to dashboard Cite

MSC cells are tumor cells originally induced in BALB/c mice by Moloney sarcoma virus. In these studies we demonstrated that, although these tumor cells are sensitive in vitro both to lysis by NK or NK-like cells and to the growth-inhibitory effect of murine L-cell interferon (IFN), the growth of the tumor in vivo could be either inhibited or enhanced by IFN. The outcome of in vivo IFN treatment was dependent on the timing and route of IFN administration relative to tumor challenge. IFN given systematically at the same time as tumor challenge resulted in enhancement of primary tumor formation, rate of tumor growth and subsequent progressive tumor growth. In contrast, IFN administered at the site of tumor inoculation on days 1-3 after tumor challenge inhibited tumor formation and growth. Histopathology of tissue sections obtained from the site of tumor challenge confirmed these results. Similar studies performed in mice given 450 rads of X-irradiation showed that IFN could still inhibit tumor growth when administered at the site of tumor inoculation on days 1-3 after tumor challenge. IFN administered simultaneously with tumor challenge, however, did not enhance tumor growth in irradiated mice. These results are consistent with the interpretation that 1) inhibition of MSC-induced tumor growth by IFN has a radioresistant component and 2) the enhancement of MSC-induced tumor formation by IFN is dependent on interaction with a radiosensitive population of cells, possibly lymphoid cells.

show abstract

Development and persistence of cytolytic T lymphocytes in regressing or progressing moloney sarcomas

Cited by 16 publications

References 13 publications

Resurgence of killing and in vivo protection mediated by lymphocytes cultured from lymph nodes draining Moloney sarcomas

Resurgence of killing and in vivo protection mediated by lymphocytes cultured from lymph nodes draining Moloney sarcomas

Characterization of lymphocyte subsets in spontaneous mouse mammary tumors and host lymphoid organs

Enhancement or inhibition of tumor growth by interferon: Dependence on treatment protocol

Contact Info

Product

Resources

About