Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1993 Mar 1;177(3):741–750. doi: 10.1084/jem.177.3.741

Abnormal in vitro proliferation and differentiation of T cell colony- forming cells in patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy and healthy HTLV-I carriers

PMCID: PMC2190926  PMID: 8094736

Abstract

T cell colonies were generated from the peripheral blood mononuclear cells (PBMC) of 10 patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy (TSP/HAM), two healthy HTLV-I carriers, and 17 healthy HTLV-I- seronegative subjects. PBMC were cultured in methylcellulose in the absence of added growth factors (spontaneous T cell colonies), or in the presence of phorbol myristate acetate and interleukin 2 (induced T cell colonies). PBMC T cell colony-forming cells (T-CFC) from all TSP/HAM patients and HTLV-I carriers were able to grow in the absence of added growth factors and/or mitogenic stimulation. Pooled spontaneous and induced colonies were composed of cells bearing CD3+, CD4+, CD8+, and CD1+ antigens. Colonies from normal HTLV-I-seronegative subjects displayed mature cells bearing the CD3+, CD4+, CD8+, and CD1- surface phenotype. In addition, spontaneous and induced T cell colonies expressed HTLV-I antigens in 18-38% of the cells from TSP/HAM patients and HTLV-I carriers. These results demonstrate that HTLV-I infection is associated with an abnormal proliferation and differentiation of T cell progenitors in vitro and that the T-CFC from HTLV-I-seropositive individuals are infected, suggesting that T-CFC abnormalities may play a predominant role in the pathophysiology of HTLV-I.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernstein M. L., Winkelstein A., Dobson S. A. Depressed T cell colony growth in systemic lupus erythematosus. Arthritis Rheum. 1980 Apr;23(4):385–391. doi: 10.1002/art.1780230401. [DOI] [PubMed] [Google Scholar]
  2. Bever C. T., Jr, McFarland H. F., Levy H. B., McFarlin D. E. Cortisol induction by poly ICLC: implications for clinical trials of interferon. Ann Neurol. 1988 Feb;23(2):196–199. doi: 10.1002/ana.410230215. [DOI] [PubMed] [Google Scholar]
  3. Claësson M. H., Rodger M. B., Johnson G. R., Whittingham S., Metcalf D. Colony formation by human T lymphocytes in agar medium. Clin Exp Immunol. 1977 Jun;28(3):526–534. [PMC free article] [PubMed] [Google Scholar]
  4. Duc Dodon M., Gazzolo L. Loss of interleukin-2 requirement for the generation of T colonies defines an early event of human T-lymphotropic virus type I infection. Blood. 1987 Jan;69(1):12–17. [PubMed] [Google Scholar]
  5. Fibach E., Gerassi E., Sachs L. Induction of colony formation in vitro by human lymphocytes. Nature. 1976 Jan 15;259(5539):127–129. doi: 10.1038/259127a0. [DOI] [PubMed] [Google Scholar]
  6. Georgoulias V., Auclair H., Jasmin C. Heterogeneity of peripheral blood T-cell colony-forming cells in patients with T-cell malignancies. Leuk Res. 1984;8(6):1025–1036. doi: 10.1016/0145-2126(84)90057-2. [DOI] [PubMed] [Google Scholar]
  7. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  8. Gessain A., Louie A., Gout O., Gallo R. C., Franchini G. Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy. J Virol. 1991 Mar;65(3):1628–1633. doi: 10.1128/jvi.65.3.1628-1633.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gessain A., Saal F., Gout O., Daniel M. T., Flandrin G., de The G., Peries J., Sigaux F. High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis. Blood. 1990 Jan 15;75(2):428–433. [PubMed] [Google Scholar]
  10. Gout O., Baulac M., Gessain A., Semah F., Saal F., Périès J., Cabrol C., Foucault-Fretz C., Laplane D., Sigaux F. Rapid development of myelopathy after HTLV-I infection acquired by transfusion during cardiac transplantation. N Engl J Med. 1990 Feb 8;322(6):383–388. doi: 10.1056/NEJM199002083220607. [DOI] [PubMed] [Google Scholar]
  11. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., 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 U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Itoyama Y., Minato S., Kira J., Goto I., Sato H., Okochi K., Yamamoto N. Altered subsets of peripheral blood lymphocytes in patients with HTLV-I associated myelopathy (HAM). Neurology. 1988 May;38(5):816–818. doi: 10.1212/wnl.38.5.816. [DOI] [PubMed] [Google Scholar]
  13. Itoyama Y., Minato S., Kira J., Goto I., Sato H., Okochi K., Yamamoto N. Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy. Neurology. 1988 Aug;38(8):1302–1307. doi: 10.1212/wnl.38.8.1302. [DOI] [PubMed] [Google Scholar]
  14. Lunardi Iskandar Y., Georgoulias V., Rozenbaum W., Vittecoq D., Meyer P., Gentilini M., Jasmin C. AIDS and lymphadenopathy syndrome (LAS) patients display similar abnormal in vitro proliferation and differentiation of T-colony forming cells (T-CFC). Cancer Detect Prev Suppl. 1987;1:525–533. [PubMed] [Google Scholar]
  15. Lunardi-Iskandar Y., Georgoulias V., Allouche M., Rozenbaum W., Klatzmann D., Coll M. C., Meyer P., Gluckman J. C., Gentilini M., Jasmin C. Abnormal in vitro proliferation and differentiation of T colony forming cells in AIDS patients and clinically normal male homosexuals. Clin Exp Immunol. 1985 May;60(2):285–293. [PMC free article] [PubMed] [Google Scholar]
  16. Lunardi-Iskandar Y., Georgoulias V., Rozenbaum W., Klatzmann D., Coll M. C., Meyer P., Gentilini M., Gluckman J. C., Jasmin C. Abnormal in vitro proliferation and differentiation of T colony-forming cells in patients with lymphadenopathy syndrome. Blood. 1986 Apr;67(4):1063–1069. [PubMed] [Google Scholar]
  17. Lunardi-Iskandar Y., Georgoulias V., Vittecoq D., Nugeyre M. T., Ammar A., Clemenceau C., Barre-Sinoussi F., Chermann J. C., Schwartzenberg L., Jasmin C. Peripheral blood adherent cells from AIDS patients inhibit normal T-colony growth through decreased expression of interleukin 2-receptors and production of interleukin 2. Leuk Res. 1987;11(8):753–760. doi: 10.1016/0145-2126(87)90013-0. [DOI] [PubMed] [Google Scholar]
  18. Lunardi-Iskandar Y., Nugeyre M. T., Georgoulias V., Barré-Sinoussi F., Jasmin C., Chermann J. C. Replication of the human immunodeficiency virus 1 and impaired differentiation of T cells after in vitro infection of bone marrow immature T cells. J Clin Invest. 1989 Feb;83(2):610–615. doi: 10.1172/JCI113924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Madsen M., Johnsen H. E. A methodological study of E-rosette formation using AET-treated sheep red blood cells. J Immunol Methods. 1979 May 10;27(1):61–74. doi: 10.1016/0022-1759(79)90239-4. [DOI] [PubMed] [Google Scholar]
  20. Martin L. H., Calabi F., Lefebvre F. A., Bilsland C. A., Milstein C. Structure and expression of the human thymocyte antigens CD1a, CD1b, and CD1c. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9189–9193. doi: 10.1073/pnas.84.24.9189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Osame M., Matsumoto M., Usuku K., Izumo S., Ijichi N., Amitani H., Tara M., Igata A. Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells. Ann Neurol. 1987 Feb;21(2):117–122. doi: 10.1002/ana.410210203. [DOI] [PubMed] [Google Scholar]
  22. Osame M., Usuku K., Izumo S., Ijichi N., Amitani H., Igata A., Matsumoto M., Tara M. HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986 May 3;1(8488):1031–1032. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  23. Poiesz B. J., Ruscetti F. W., Reitz M. S., Kalyanaraman V. S., Gallo R. C. Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sézary T-cell leukaemia. Nature. 1981 Nov 19;294(5838):268–271. doi: 10.1038/294268a0. [DOI] [PubMed] [Google Scholar]
  24. Ragni M. V., Winkelstein A., Evans T. L., Lewis J. H., Bontempo F. A., Spero J. A., Rabin B. S. T lymphocyte colony assay in hemophiliacs. Blood. 1984 Jul;64(1):105–109. [PubMed] [Google Scholar]
  25. Rodgers-Johnson P., Gajdusek D. C., Morgan O. S., Zaninovic V., Sarin P. S., Graham D. S. HTLV-I and HTLV-III antibodies and tropical spastic paraparesis. Lancet. 1985 Nov 30;2(8466):1247–1248. doi: 10.1016/s0140-6736(85)90778-0. [DOI] [PubMed] [Google Scholar]
  26. Rozenszajn L. A., Shoham D., Kalechman I. Clonal proliferation of PHA-stimulated human lymphocytes in soft agar culture. Immunology. 1975 Dec;29(6):1041–1055. [PMC free article] [PubMed] [Google Scholar]
  27. Sutherland D. C., Dalton G., Wilson J. D. T-lymphocyte colonies in malignant disease. Lancet. 1976 Nov 20;2(7995):1113–1115. doi: 10.1016/s0140-6736(76)91089-8. [DOI] [PubMed] [Google Scholar]
  28. Tendler C. L., Greenberg S. J., Blattner W. A., Manns A., Murphy E., Fleisher T., Hanchard B., Morgan O., Burton J. D., Nelson D. L. Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5218–5222. doi: 10.1073/pnas.87.13.5218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Triebel F., Robinson W. A., Hayward A. R., Goube de Laforest P. G. Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T-lymphocyte lineage. Blood. 1981 Nov;58(5):911–915. [PubMed] [Google Scholar]
  30. Uchiyama T., Yodoi J., Sagawa K., Takatsuki K., Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481–492. [PubMed] [Google Scholar]
  31. Winkelstein A., Klein R. S., Evans T. L., Dixon B. W., Holder W. L., Weaver L. D. Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome. J Immunol. 1985 Jan;134(1):151–156. [PubMed] [Google Scholar]
  32. Yasuda K., Sei Y., Yokoyama M. M., Tanaka K., Hara A. Healthy HTLV-I carriers in Japan: the haematological and immunological characteristics. Br J Haematol. 1986 Sep;64(1):195–203. doi: 10.1111/j.1365-2141.1986.tb07587.x. [DOI] [PubMed] [Google Scholar]
  33. Yoshida M., Seiki M., Yamaguchi K., 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 U S A. 1984 Apr;81(8):2534–2537. doi: 10.1073/pnas.81.8.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES