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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Mar;86(3):322–328. doi: 10.1111/j.1349-7006.1995.tb03058.x

Detection of Homing, Proliferation, and Infiltration Sites of Adult T Cell Leukemia Cells in Severe Combined Immunodeficiency Mice Using Radiometric Techniques

Akifumi Takaori‐Kondo 1,2, Makoto Hosono 3, Kazunori Imada 1,2, Zheng‐Sheng Yao 3, Harumi Sakahara 3, Hirohiko Yamabe 4, Junji Konishi 3, Minoru Okuma 2, Takashi Uchiyama 1,
PMCID: PMC5920819  PMID: 7744703

Abstract

To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL‐43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected 111In‐oxine‐labeled ATL‐43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3±9.4 and 10.0±3.6 % injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1±2.5 and 3.7±0.9 %ID/g, respectively). Next, we injected radiolabeled anti‐Tac monoclonal antibody (MoAb) recognizing human interleukin‐2 receptor (IL‐2R) α chain or isotype‐matched control MoAb RPC5 in SCID mice bearing ATL‐43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with 125I‐labeled anti‐Tac MoAb (22.5±6.9 and 22.8±9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with 125I‐labeled RPC5 MoAb (12.0±5.1 and 7.5±4.6 %ID/g, respectively). Similar results were obtained with 111In‐labeled anti‐Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL‐43T cells, indicating that ATL‐43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL‐43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti‐Tac MoAb.

Keywords: Adult T cell leukemia, Human T cell leukemia virus type I, Severe combined immunodeficiency mice, Anti‐Tac monoclonal antibody, Radioimmunoscintigraphy

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REFERENCES

  • 1).Uchiyama , T. , Yodoi , J. , Sagawa , K. , Takatsuki , K. and Uchino , H.Adult T‐cell Jeukemia: clinical and hematological features of 16 cases . Blood , 50 , 481 – 492 ( 1977. ). [PubMed] [Google Scholar]
  • 2).Takatsuki , K. , Uchiyama , T. , Sagawa , K. and Yodoi , J.Adult T cell leukemia in Japan . In “ Topics in Hematology ” ed. Seno S. , Takaku F. and Irino S. , pp . 73 – 77 ( 1977. ). Excerpta Medica; , Amsterdam . [Google Scholar]
  • 3).Poiesz , B. J. , Ruscetti , F. W. , Gazdar , A. F. , Bunn , P. A. , Minna , J. D. and Gallo , R. C.Detection and isolation of type‐C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T‐cell lymphoma . Proc. Natl. Acad. Sci. USA , 77 , 7415 – 7419 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4).Hinuma , Y. , Nagata , K. , Hanaoka , M. , Nakai , M. , Matsumoto , T. , Kinoshita , K. , Shirakawa , S , and Miyoshi , I.Adult T‐cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera . Proc. Natl. Acad. Sci. USA , 78 , 6476 – 6480 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5).Yoshida , M. , Seiki , M. , Yamaguchi , K. and Takatsuki , K.Monoclonal integration of human T‐cell leukemia provirus in all primary tumors of adult T‐cell leukemia suggests causative role of human T‐cell leukemia virus in the disease . Proc. Natl. Acad. Sci. USA , 81 , 2534 – 2537 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6).Ishikawa , T. , Imura , A. , Tanaka , K. , Shirane , H. , Okuma , M. and Uchiyama , T.E‐Selectin and vascular cell adhesion molecule‐1 mediate adult T‐cell leukemia cell adhesion to endothelial cells . Blood , 82 , 1590 – 1598 ( 1993. ). [PubMed] [Google Scholar]
  • 7).Kondo , A. , Imada , K. , Hattori , T. , Yamabe , H. , Tanaka , T. , Miyasaka , M. , Okuma , M. and Uchiyama , T.A model of in vivo cell proliferation of adult T‐cell leukemia . Blood , 82 , 2501 – 2509 ( 1993. ). [PubMed] [Google Scholar]
  • 8).Hattori , T. , Asou , N. , Suzushima , H. , Takatsuki , K. , Tanaka , K. , Naito , K. , Natori , H. and Oizumi , K.Leukaemia of novel gastrointestinal T‐lymphocyte population infected with HTLV‐I . Lancet , 337 , 76 – 77 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 9).Bosma , G. C. , Custer , R. P. and Bosma , M. J.A severe combined immunodeficiency mutation in the mouse . Nature , 30 , 527 – 530 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 10).Uchiyama , T. , Broder , S. and Waldmann , T. A.A monoclonal antibody (anti‐Tac) reactive with activated and functionally mature human T cells. I. Production of anti‐Tac monoclonal antibody and distribution of Tac(+) cells . J. Immunol. , 126 , 1393 – 1397 ( 1981. ). [PubMed] [Google Scholar]
  • 11).Uchiyama , T. , Nelson , D. L. , Fleisher , T. A. and Waldmann , T. A.A monoclonal antibody (anti‐Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic T cells, suppressor cells, and on one of two types of helper T cells . J. Immunol. , 126 , 1398 – 1403 ( 1981. ). [PubMed] [Google Scholar]
  • 12).Tsudo , M. , Uchiyama , T. and Uchino , H.Expression of Tac antigen on activated normal human B cells . J. Exp. Med. , 160 , 612 – 617 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13).Uchiyama , T. , Hori , T. , Tsudo , M. , Wano , Y. , Umadome , H. , Tamori , S. , Yodoi , J. , Maeda , M. , Sawami , H. and Uchino , H.Interleukin‐2 receptor (Tac antigen) expressed on adult T cell leukemia cells . J. Clin. Invest. , 76 , 446 – 453 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14).Tsudo , M. , Uchiyama , T. , Uchino , H. and Yodoi , J.Failure of regulation of Tac antigen/TCGF receptor on adult T cell leukemia cells by anti‐Tac monoclonal antibody . Blood , 61 , 1014 – 1016 ( 1983. ). [PubMed] [Google Scholar]
  • 15).Hunter , W. N. and Greenwood , F. C.Preparation of iodine‐131 labeled human growth hormone of high specific activity . Nature , 194 , 495 – 496 ( 1962. ). [DOI] [PubMed] [Google Scholar]
  • 16).Hnatowich , D. J. , Childs , R. L. , Lanteigne , D. and Najafi , A.The preparation of DTPA‐coupled antibodies radiolabeled with metallic radionuclides: an improved method . J. Immunol. Methods , 65 , 147 – 157 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 17).Saga , T. , Endo , K. , Akiyama , T. , Sakahara , H. , Koizumi , M. , Watanabe , Y. , Nakai , T. , Hosono , M. , Yamamoto , T. , Toyoshima , K. and Konishi , J.Scintigraphic detection of overexpressed c‐erbB‐2 protooncogene products by a class‐switched murine anti‐c‐erbB‐2 protein monoclonal antibody . Cancer Res. , 51 , 990 – 994 ( 1991. ). [PubMed] [Google Scholar]
  • 18).Scatchard , G.The attraction of proteins for small molecules and ions . Ann. N.Y. Acad. Sci. , 51 , 660 – 672 ( 1949. ). [Google Scholar]
  • 19).McCarthy , K. , Velchik , M. G. , Alavi , A. , Mandell , G. A. , Esterhai , J. L. and Goll , S.Indium‐111‐labeled white blood cells in the detection of osteomyelitis complicated by a pre‐existing condition . J. Nucl. Med. , 29 , 1015 – 1021 ( 1988. ). [PubMed] [Google Scholar]
  • 20).Shirono , K. , Hattori , T. , Hata , H. , Nishimura , H. and Takatsuki , K.Profiles of expression of activated cell antigens on peripheral blood and lymph node cells from different clinical stages of adult T‐cell leukemia . Blood , 73 , 1664 – 1671 ( 1989. ). [PubMed] [Google Scholar]
  • 21).Hamada , T. , Setoyama , M. , Katahira , Y. , Furuno , T. , Fujiyoshi , T. , Sonoda , S. and Tashiro , M.Differences in HTLV‐I integration patterns between skin lesions and peripheral blood lymphocytes of HTLV‐I seropositive patients with cutaneous lymphoproliferative disorders . J. Dermatol. Sci. , 4 , 76 – 82 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 22).Dosaka , N. , Tanaka , T. , Miyachi , Y. , Imamura , S. and Kakizuka , A.Examination of HTLV‐I integration in the skin lesions of various types of adult T‐cell leukemia (ATL): independence of cutaneous‐type ATL confirmed by Southern blot analysis . J. Invest. Dermatol. , 96 , 196 – 200 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 23).Brown , B. A. , Comeau , R. D. , Jones , P. L. , Liberatore , F. A. , Neacy , W. P. , Sands , H. and Gallagher , B. M.Pharmacokinetics of the monoclonal antibody B72.3 and its fragments labeled with either 125In . Cancer Res. , 47 , 1149 – 1154 ( 1987. ). [PubMed] [Google Scholar]
  • 24).Carrasqillo , J. A. , Mulshine , J. L. , Bunn , P. A. , Jr. , Reynolds , J. C. , Foon , K. A. , Schroff , R. W. , Perentesis , P. , Steis , R. G. , Keenan , A. M. , Horowitz , M. and Larson , S. M.Indium‐111 T101 monoclonal antibody is superior to iodine‐131 T101 in imaging of cutaneous T‐cell lymphoma . J. Nucl. Med. , 28 , 281 – 287 ( 1987. ). [PubMed] [Google Scholar]
  • 25).Uchiyama , T. , Kondo , A. , Kiyokawa , T. , Yamaguchi , K. , Murphy , J. R. and Takatsuki , K.Interleukin 2 receptortargeted therapy of ATL . Gann Monogr. Cancer Res. , 40 , 125 – 133 ( 1993. ). [Google Scholar]
  • 26).Kreitman , R. J. , Chaudhary , V. K. , Waldmann , T. A. , Willingham , M. C. , FitzGerald , D. J. and Pastan , I.There‐combinant immunotoxin anti‐Tac(Fv)‐Pseudomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T‐cell leukemia . Proc. Natl. Acad. Sci. USA , 87 , 8291 – 8295 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27).Kiyokawa , T. , Shirono , K. , Hattori , T. , Nishimura , H. , Yamaguchi , K. , Nichols , J. C. , Strom , T. B. , Murphy , J. R. and Takatsuki , K.Cytotoxicity of interleukin 2‐toxin toward lymphocytes from patients with adult T‐cell leukemia . Cancer Res. , 49 , 4042 – 4046 ( 1989. ). [PubMed] [Google Scholar]
  • 28).Waldmann , T. A. , White , J. D. , Goldman , C. K. , Top , L. , Grant , A. , Bamford , R. , Roessler , E. , Horak , I. D. , Zaknoen , S. , Kasten‐Sportes , C. , England , R. , Horak , E. , Mishra , B. , Dipre , M. , Hale , P. , Fleisher , T. A. , Junghans , R. P. , Jaffe , E. S. and Nelson , D. L.The interleukin‐2 receptor: a target for monoclonal antibody treatment of human T‐cell lymphotrophic virus I‐induced adult T‐cell leukemia . Blood , 82 , 1701 – 1712 ( 1993. ). [PubMed] [Google Scholar]
  • 29).Waldmann , T. A. , Pastan , I. H. , Gansow , O. A. and Junghans , R. P.The multichain interleukin‐2 receptor: a target for immunotherapy . Ann. Intern. Med. , 116 , 148 – 160 ( 1992. ). [DOI] [PubMed] [Google Scholar]

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