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Evaluation of in vivo and in vitro effectivity of immune defense against a spontaneously arising, nonlymphoid rat tumor

II. T cell response after induction of immunogenicity

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Summary

It was evaluated in vitro whether it is possible to induce immunogenicity by haptenization of a nonlymphoid rat tumor, BSp6AS, which is known to be antigenic, but non-immunogenic, in the syngeneic host. The effectivity of ‘induced immunogenicity’ was tested in vivo.

BSp6AS, an NK- and macrophage-resistant variant of a spontaneously arising fibrosarcoma in the BDX rat strain, does not induce a primary or a secondary T cell response after in vivo or in vitro priming. This deficiency in cytotoxic response is due solely to failure of activation of helper T cells (TH), since (a) cytotoxic T cells (CTL) can be detected after in vitro stimulation in the presence of interleukin 2 (IL-2)-containing medium; and (b) there are no indications for down-regulation of a potential specific immune response by suppressor T cells (TS). The lack of activation of tumor-specific TH can be bypassed by activation of hapten-specific TH. Upon coculture with haptenized tumor cells as a stimulator population, both hapten-specific and tumor-specific CTL are activated by hapten-specific TH.

In line with the findings in vitro, no transplant rejection of naive tumor cells was seen after a variety of immunization schedules. But immunized F1 hybrids did reject tumor grafts, supporting the hypothesis of lacking help in the syngeneic situation. This could be confirmed in the syngeneic system by adoptive transfer experiments. Tumor-specific CTL, educated in vitro in the presence of IL-2, were ineffective. But complete protection against haptenized, and partial protection against native tumor cells was achieved in the additional presence of hapten-specific TH.

To our knowledge these experiments prove for the first time that hapten-specific TH are efficient in inducing an immune response even against a nonlymphoid, nonimmunogenic tumor, i.e., it is possible (a) to activate tumor-specific CTL and (b) to initiate tumor graft rejection via hapten-specific TH.

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Abbreviations

BSS:

Hank's balanced salt solution

CFA:

complete Freund's adjuvant

ConA:

Concanavalin A

CTL:

cytotoxic T cell

iFA:

incomplete FA

IL-2:

interleukin 2-containing supernatant of rat spleen cells cultured in ConA

IP:

intraperitoneal

IV:

intravenous

LNC:

lymph node cells

2-ME:

2-mercaptoethanol

MHC:

major histocompatibility complex

MLTC:

mixed lymphocyte tumor cell culture

RPMI 1640:

supplemented with antibiotics, L-glutamine and fetal calf serum

SC:

spleen cells

SC:

subcutaneous

TAA:

tumor-associated antigen(s)

TB:

tumor bearer

TD100 :

tumor cell dose resulting in 100% takes

TH :

helper T cells

TS :

suppressor T cells

TNBS:

trinitrobenzenesulfonic acid

TNP:

trinitrophenyl

WAB:

Wistar Nottingham rats

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  1. Institute of Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, D-6900, Heidelberg, Federal Republic of Germany

    Margot Zöller

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Zöller, M. Evaluation of in vivo and in vitro effectivity of immune defense against a spontaneously arising, nonlymphoid rat tumor. Cancer Immunol Immunother 19, 189–197 (1985). https://doi.org/10.1007/BF00199225

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  • DOI: https://doi.org/10.1007/BF00199225

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