Abstract
The results of studies on the reticulum cell sarcoma (RCS) tumors of SJL/J mice presented here, indicate that spontaneous tumors, which arise in older mice, also possess the capacity to induce the vigorous proliferative response in syngenetic T lymphocytes that are characteristic of the transplantable RCS lines. Analysis of cell surface antigens revealed the presence of Ia determinats on gradient- purified transplantable RCS tumor cells; however, these cells did not express Thy 1.2, nIg, or, any of the viral proteins that were tested for by specific antisera. Pretreatment of RCS cells with anti-Ia sera and complement-deleted cells that were stimulatory for syngenetic T lymphocytes, and addition of anti-Ia sera directly to cultures blocked the proliferative response at the stimulator (RCS) cell level. Lymph node cells from H-2(8) strains other than SJL/J, including A.SW and B10.S also gave proliferative responses to RCS cells, although lower in magnitude. A requirement on the part of responding cells for identity with RCS cells at the Ir region was indicated by the finding that A.TH but not A.TL lymph node cells responded to RCS. It is concluded that RCS cells stimulate Ir-region identical T cells (without evidence of presensitization) through a modification in the expression of Ia antigens on the surface of the tumor cells.
Full Text
The Full Text of this article is available as a PDF (997.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BOYSE E. A., OLD L. J., CHOUROULINKOV I. CYTOTOXIC TEST FOR DEMONSTRATION OF MOUSE ANTIBODY. Methods Med Res. 1964;10:39–47. [PubMed] [Google Scholar]
- Batzing B. L., Yurconic M., Jr, Hanna M. G., Jr Autogenous immunity to endogenous RNA tumor virus: chronic humoral immune response to virus envelope antigens in B6C3F1 mice. J Natl Cancer Inst. 1974 Jan;52(1):117–131. doi: 10.1093/jnci/52.1.117. [DOI] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carswell E. A., Lerman S. P., Thorbecke G. J. Properties of reticulum cell sarcomas in SJL/J mice. II. Fate of labeled tumor cells in normal and irradiated syngeneic mice. Cell Immunol. 1976 Apr;23(1):39–52. doi: 10.1016/0008-8749(76)90170-2. [DOI] [PubMed] [Google Scholar]
- Carswell E. A., Wanebo H. J., Old L. J., Boyse E. A. Immunogenic properties of reticulum cell sarcomas of SJL/J mice. J Natl Cancer Inst. 1970 Jun;44(6):1281–1288. [PubMed] [Google Scholar]
- Chang K. S., Aoki T., Law L. W. Isolation of a B-tropic type-C virus from reticulum cell neoplasms induced in BALB/c mice by SJL/J type-C virus. J Natl Cancer Inst. 1975 Jan;54(1):83–87. [PubMed] [Google Scholar]
- Cohen A., Schlesinger M. Absorption of guinea pig serum with agar. A method for elimination of itscytotoxicity for murine thymus cells. Transplantation. 1970 Jul;10(1):130–132. doi: 10.1097/00007890-197007000-00027. [DOI] [PubMed] [Google Scholar]
- Cornelius E. A. Rapid viral induction of murine lymphomas in the graft-versus-host reaction. J Exp Med. 1972 Dec 1;136(6):1533–1544. doi: 10.1084/jem.136.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- David C. S., Shreffler D. C., Frelinger J. A. New lymphocyte antigen system (Lna) controlled by the Ir region of the mouse H-2 complex. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2509–2514. doi: 10.1073/pnas.70.9.2509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Festenstein H. Pertinent features of M locus determinants including revised nomenclature and strain distribution. Transplantation. 1974 Dec;18(6):555–557. [PubMed] [Google Scholar]
- Gardner I. D., Bowern N. A., Blanden R. V. Cell-medicated cytotoxicity against ectromelia virus-infected target cells. III. Role of the H-2 gene complex. Eur J Immunol. 1975 Feb;5(2):122–127. doi: 10.1002/eji.1830050210. [DOI] [PubMed] [Google Scholar]
- Hammerling U., Chin A. F., Abbott J., Scheid M. P. The ontogeny of murine B lymphocytes. I. Induction of phenotypic conversion of Ia-to Ia+ lymphocytes. J Immunol. 1975 Nov;115(5):1425–1431. [PubMed] [Google Scholar]
- Howe M. L., Goldstein A. L., Battisto J. R. Isogeneic lymphocyte interaction: recognition of self antigens by cells of the neonatal thymus. Proc Natl Acad Sci U S A. 1970 Oct;67(2):613–619. doi: 10.1073/pnas.67.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huber B., Cantor H., Shen F. W., Boyse E. A. Independent differentiative pathways of Ly1 and Ly23 subclasses of T cells. Experimental production of mice deprived of selected T-cell subclasses. J Exp Med. 1976 Oct 1;144(4):1128–1133. doi: 10.1084/jem.144.4.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kano S., Bloom B. R., Shreffler D. C. Blocking of MLC stimulation by anti-Ia sera: studies with the virus plaque assay. J Immunol. 1976 Jul;117(1):242–245. [PubMed] [Google Scholar]
- Katz D. H., Hamaoka T., Dorf M. E., Maurer P. H., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. IV. Involvement of the immune response (Ir) gene in the control of lymphocyte interactions in responses controlled by the gene. J Exp Med. 1973 Sep 1;138(3):734–739. doi: 10.1084/jem.138.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knight S. T., Thorbecke G. J. Ontogeny of cellular immunity: development in rat thymocytes of mixed lymphocyte reactivity to allogeneic and xenogeneic cells. Cell Immunol. 1971 Feb;2(1):91–100. doi: 10.1016/0008-8749(71)90028-1. [DOI] [PubMed] [Google Scholar]
- Kuntz M. M., Innes J. B., Weksler M. E. Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes. J Exp Med. 1976 May 1;143(5):1042–1054. doi: 10.1084/jem.143.5.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lerman S. P., Chapman J. M., Carswell E. A., Thorbecke G. J. Properties of reticulum-cell sarcomas in SJL/J mice. I. Proliferative response to tumor cells of T-derived lymphoid cells from normal mice. Int J Cancer. 1974 Dec 15;14(6):808–816. doi: 10.1002/ijc.2910140615. [DOI] [PubMed] [Google Scholar]
- Loos J. A., Roos D. Ficoll-isopaque gradients for the determination of density distributions of human blood lymphocytes and other reticulo-endothelial cells. Exp Cell Res. 1974 Jun;86(2):333–341. doi: 10.1016/0014-4827(74)90721-6. [DOI] [PubMed] [Google Scholar]
- Meo T., David C. S., Nabholz M., Miggiano V., Shreffler D. C. Demonstration by MLR test of a previously unsuspected intra-H-2 crossover in the B10.HTT strain: implications concerning location of MLR determinants in the Ir region. Transplant Proc. 1973 Dec;5(4):1507–1510. [PubMed] [Google Scholar]
- Murphy D. B., Herzenberg L. A., Okumura K., Herzenberg L. A., McDevitt H. O. A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med. 1976 Sep 1;144(3):699–712. doi: 10.1084/jem.144.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nabholz M., Young H., Rynbeek A., Boccardo R., David C. S., Meo T., Miggiano V., Shreffler D. C. I-region-associated determinants: expression on mitogen-stimulated lymphocytes and detection by cytotoxic T cells. Eur J Immunol. 1975 Sep;5(9):594–599. doi: 10.1002/eji.1830050903. [DOI] [PubMed] [Google Scholar]
- Niederhuber J. E., Frelinger J. A., Dugan E., Coutinho A., Shreffler D. C. Effects of anti-Ia serum on mitogenic responses. I. Inhibition of the proliferative response to B cell mitogen, LPS, by specific anti-Ia sera. J Immunol. 1975 Dec;115(6):1672–1676. [PubMed] [Google Scholar]
- Nowinski R. C., Kaehler S. L. Antibody to leukemia virus: widespread occurrence in inbred mice. Science. 1974 Sep 6;185(4154):869–871. doi: 10.1126/science.185.4154.869. [DOI] [PubMed] [Google Scholar]
- Nowinski R. C., Klein P. A. Anomalous reactions of mouse alloantisera with cultured tumor cells. II. Cytotoxicity is caused by antibodies to leukemia viruses. J Immunol. 1975 Nov;115(5):1261–1268. [PubMed] [Google Scholar]
- Opelz G., Kiuchi M., Takasugi M., Terasaki P. I. Autologous stimulation of human lymphocyte subpopulation. J Exp Med. 1975 Nov 1;142(5):1327–1333. doi: 10.1084/jem.142.5.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poe W. J., Michael J. G. The effect of serum inhibitor on the antigenic and mitogenic responses to E. coli bacteria. J Immunol. 1976 Apr;116(4):1129–1133. [PubMed] [Google Scholar]
- Romano T. J., Mond J. J., Thorbecke G. J. Immunological memory function of the T and B cell types: distribution over mouse spleen and lymph nodes. Eur J Immunol. 1975 Mar;5(3):211–215. doi: 10.1002/eji.1830050312. [DOI] [PubMed] [Google Scholar]
- Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruhl H., Shevach E. M. The effect of alloantisera on antigen-induced T cell proliferation. J Immunol. 1975 Dec;115(6):1493–1499. [PubMed] [Google Scholar]
- Röllinghoff M., Pfizenmeier K., Trostmann H., Wagner H. T cell proliferation in the mixed lymphocyte culture does not necessarily result in the generation of cytotoxic T effector cells. Eur J Immunol. 1975 Aug;5(8):560–564. doi: 10.1002/eji.1830050811. [DOI] [PubMed] [Google Scholar]
- Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
- Shiku H., Takahashi T., Bean M. A., Old L. J., Oettgen H. F. Ly phenotype of cytotoxic T cells for syngeneic tumor. J Exp Med. 1976 Oct 1;144(4):1116–1120. doi: 10.1084/jem.144.4.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shreffler D. C., David C. S. The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization. Adv Immunol. 1975;20:125–195. doi: 10.1016/s0065-2776(08)60208-4. [DOI] [PubMed] [Google Scholar]
- Siegler R., Rich M. A. Pathogenesis of reticulum cell sarcoma in mice. J Natl Cancer Inst. 1968 Jul;41(1):125–143. [PubMed] [Google Scholar]
- Stockert E., Old L. J., Boyse E. A. The G-IX system. A cell surface allo-antigen associated with murine leukemia virus; implications regarding chromosomal integration of the viral genome. J Exp Med. 1971 Jun 1;133(6):1334–1355. doi: 10.1084/jem.133.6.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T., Taniguchi M., David C. S. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976 Sep 1;144(3):713–725. doi: 10.1084/jem.144.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weksler M. E. Lymphocyte transformation induced by autologous cells. II. Stimulation by mitogen-induced lymphoblasts. J Exp Med. 1973 Mar 1;137(3):799–806. doi: 10.1084/jem.137.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]