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. 1995 May;2(3):349–355. doi: 10.1128/cdli.2.3.349-355.1995

Infection with human T-lymphotropic virus types I and II results in alterations of cellular receptors, including the up-modulation of T-cell counterreceptors CD40, CD54, and CD80 (B7-1).

C S Dezzutti 1, D L Rudolph 1, R B Lal 1
PMCID: PMC170158  PMID: 7545080

Abstract

To examine the phenotypic alterations associated with human T-lymphotropic virus types I and II (HTLV-I and -II) infection, long-term cell lines (n = 12 HTLV-I cell lines; n = 11 HTLV-II cell lines; n = 6 virus-negative cell lines) were analyzed for the cell surface expression of various lineage markers (i.e., myeloid, progenitor, and leukocyte), integrin receptors, and receptor-counterreceptor (R-CR) pairs responsible for cellular activation. As expected, all cell lines expressed the markers characterizing the leukocyte lineage (CD43, CD44, and CD53). Of the progenitor-myeloid markers examined (CD9, CD13, CD33, CD34, and CD63), only the percent expression of CD9 was significantly increased on HTLV-I and -II-infected cell lines as compared with that on virus-negative cell lines. Analysis of the beta 1 integrin subfamily (CD29, CD49b, CD49d, CD49e, and CD49f) showed no significant change, except that CD49e was significantly decreased on the HTLV-infected cell lines. For the beta 2 integrin subfamily, the cell surface density was increased for CD18 and CD11a, while the CD11c molecule was expressed exclusively on the HTLV-I- and HTLV-II-infected cell lines. Analysis of several R-CR pairs (CD2-CD58, CD45RO-CD22, CD5-CD72, CD11a-CD54, gp39-CD40, and CD28-CD80) demonstrated that comparable levels of expression of the Rs (CD2, CD45RO, CD5, and CD28) and of some of the CRs (CD58, CD22, and CD72) were in all cell lines; however, CD54, CD40, and CD80 were expressed constitutively on the HTLV-I- and HTLV-II-infected cell lines. Functionally, the expression of these R-CR pairs did not appear to affect the autologous proliferation since monoclonal antibodies to these R-CR pairs were not able to inhibit proliferation of the infected cell lines. Taken together, our results indicate that HTLV-I and -II can modulate the expression of several T-cell activation molecules and CRs normally expressed on alternate cell types.

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Selected References

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  1. Adams R. A., Flowers A., Davis B. J. Direct implantation and serial transplantation of human acute lymphoblastic leukemia in hamsters, SB-2. Cancer Res. 1968 Jun;28(6):1121–1125. [PubMed] [Google Scholar]
  2. Bhat N. K., Adachi Y., Samuel K. P., Derse D. HTLV-1 gene expression by defective proviruses in an infected T-cell line. Virology. 1993 Sep;196(1):15–24. doi: 10.1006/viro.1993.1450. [DOI] [PubMed] [Google Scholar]
  3. Boucheix C., Benoit P., Frachet P., Billard M., Worthington R. E., Gagnon J., Uzan G. Molecular cloning of the CD9 antigen. A new family of cell surface proteins. J Biol Chem. 1991 Jan 5;266(1):117–122. [PubMed] [Google Scholar]
  4. Dezzutti C. S., Rudolph D. L., Dhawan S., Lal R. B. Modulation of HTLV-II-associated spontaneous lymphocyte proliferation by beta 2 integrin CD11a/CD18 involves interaction with its cognate ligand, CD54. Cell Immunol. 1994 Jun;156(1):113–123. doi: 10.1006/cimm.1994.1157. [DOI] [PubMed] [Google Scholar]
  5. Dezzutti C. S., Rudolph D. L., Roberts C. R., Lal R. B. Characterization of human T-lymphotropic virus type I- and II-infected T-cell lines: antigenic, phenotypic, and genotypic analysis. Virus Res. 1993 Jul;29(1):59–70. doi: 10.1016/0168-1702(93)90125-7. [DOI] [PubMed] [Google Scholar]
  6. Dhawan S., Weeks B. S., Abbasi F., Gralnick H. R., Notkins A. L., Klotman M. E., Yamada K. M., Klotman P. E. Increased expression of alpha 4 beta 1 and alpha 5 beta 1 integrins on HTLV-I-infected lymphocytes. Virology. 1993 Dec;197(2):778–781. doi: 10.1006/viro.1993.1656. [DOI] [PubMed] [Google Scholar]
  7. Fan S. T., Brian A. A., Lollo B. A., Mackman N., Shen N. L., Edgington T. S. CD11a/CD18 (LFA-1) integrin engagement enhances biosynthesis of early cytokines by activated T cells. Cell Immunol. 1993 Apr 15;148(1):48–59. doi: 10.1006/cimm.1993.1090. [DOI] [PubMed] [Google Scholar]
  8. Folks T., Benn S., Rabson A., Theodore T., Hoggan M. D., Martin M., Lightfoote M., Sell K. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539–4543. doi: 10.1073/pnas.82.13.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fukudome K., Furuse M., Fukuhara N., Orita S., Imai T., Takagi S., Nagira M., Hinuma Y., Yoshie O. Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines. Int J Cancer. 1992 Sep 30;52(3):418–427. doi: 10.1002/ijc.2910520316. [DOI] [PubMed] [Google Scholar]
  10. Gerli R., Agea E., Muscat C., Tognellini R., Fiorucci G., Spinozzi F., Cernetti C., Bertotto A. Activation of cord T lymphocytes. III. Role of LFA-1/ICAM-1 and CD2/LFA-3 adhesion molecules in CD3-induced proliferative response. Cell Immunol. 1993 Apr 15;148(1):32–47. doi: 10.1006/cimm.1993.1089. [DOI] [PubMed] [Google Scholar]
  11. Gessain A., Saal F., Giron M. L., Lasneret J., Lagaye S., Gout O., De Thé G., Sigaux F., Peries J. Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis. J Gen Virol. 1990 Feb;71(Pt 2):333–341. doi: 10.1099/0022-1317-71-2-333. [DOI] [PubMed] [Google Scholar]
  12. Haffar O. K., Smithgall M. D., Bradshaw J., Brady B., Damle N. K., Linsley P. S. Costimulation of T-cell activation and virus production by B7 antigen on activated CD4+ T cells from human immunodeficiency virus type 1-infected donors. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11094–11098. doi: 10.1073/pnas.90.23.11094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hjelle B., Appenzeller O., Mills R., Alexander S., Torrez-Martinez N., Jahnke R., Ross G. Chronic neurodegenerative disease associated with HTLV-II infection. Lancet. 1992 Mar 14;339(8794):645–646. doi: 10.1016/0140-6736(92)90797-7. [DOI] [PubMed] [Google Scholar]
  14. Höllsberg P., Wucherpfennig K. W., Ausubel L. J., Calvo V., Bierer B. E., Hafler D. A. Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells. J Immunol. 1992 May 15;148(10):3256–3263. [PubMed] [Google Scholar]
  15. Imai T., Tanaka Y., Fukudome K., Takagi S., Araki K., Yoshie O. Enhanced expression of LFA-3 on human T-cell lines and leukemic cells carrying human T-cell-leukemia virus type 1. Int J Cancer. 1993 Nov 11;55(5):811–816. doi: 10.1002/ijc.2910550520. [DOI] [PubMed] [Google Scholar]
  16. Jacobson S., Lehky T., Nishimura M., Robinson S., McFarlin D. E., Dhib-Jalbut S. Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis. Ann Neurol. 1993 Apr;33(4):392–396. doi: 10.1002/ana.410330411. [DOI] [PubMed] [Google Scholar]
  17. Kimata J. T., Palker T. J., Ratner L. The mitogenic activity of human T-cell leukemia virus type I is T-cell associated and requires the CD2/LFA-3 activation pathway. J Virol. 1993 Jun;67(6):3134–3141. doi: 10.1128/jvi.67.6.3134-3141.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kobayashi T., Miwa H., Uchida T., Matsuoka N., Kita K., Shirakawa S. Surface and cytoplasmic expression of CD2, CD13, and CD25 antigens in human T lymphotropic virus type I infected cell line. An immunoelectron microscopic study. Lab Invest. 1989 Mar;60(3):370–374. [PubMed] [Google Scholar]
  19. Koizumi S., Iwanaga M., Imai S., Yamashiro K., Mikuni C., Abe S., Kakinuma M., Saito N., Takami T., Fukazawa Y. Expression of myeloid cell phenotypes by a novel adult T-cell leukemia/lymphoma cell line. J Natl Cancer Inst. 1992 May 6;84(9):690–693. doi: 10.1093/jnci/84.9.690. [DOI] [PubMed] [Google Scholar]
  20. Koizumi S., Sugiura M., Zhang X. K., Yamashiro K., Iwanaga M., Imai S., Osato T. Simultaneous expression of T-cell and myeloid cell phenotypes in eight newly established HTLV-I-positive T-cell lines. Jpn J Cancer Res. 1992 Sep;83(9):929–932. doi: 10.1111/j.1349-7006.1992.tb02002.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lal R. B., Rudolph D. L., Rowe T., Folks T. M. Phenotypic expression of integrin membrane receptors on spontaneously proliferating CD8 cells in human T-lymphotropic virus type II (HTLV-II)-infected individuals. J Clin Immunol. 1992 Mar;12(2):75–83. doi: 10.1007/BF00918136. [DOI] [PubMed] [Google Scholar]
  22. Makgoba M. W., Sanders M. E., Ginther Luce G. E., Gugel E. A., Dustin M. L., Springer T. A., Shaw S. Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity. Eur J Immunol. 1988 Apr;18(4):637–640. doi: 10.1002/eji.1830180423. [DOI] [PubMed] [Google Scholar]
  23. Manns A., Blattner W. A. The epidemiology of the human T-cell lymphotrophic virus type I and type II: etiologic role in human disease. Transfusion. 1991 Jan;31(1):67–75. doi: 10.1046/j.1537-2995.1991.31191096189.x. [DOI] [PubMed] [Google Scholar]
  24. Minowada J., Onuma T., Moore G. E. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972 Sep;49(3):891–895. [PubMed] [Google Scholar]
  25. Mori N., Murakami S., Oda S., Eto S. Human T-cell leukemia virus type I tax induces intracellular adhesion molecule-1 expression in T cells. Blood. 1994 Jul 1;84(1):350–351. [PubMed] [Google Scholar]
  26. Smith M. R., Greene W. C. Molecular biology of the type I human T-cell leukemia virus (HTLV-I) and adult T-cell leukemia. J Clin Invest. 1991 Mar;87(3):761–766. doi: 10.1172/JCI115078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [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. Usuku K., Sonoda S., Osame M., Yashiki S., Takahashi K., Matsumoto M., Sawada T., Tsuji K., Tara M., Igata A. HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma. Ann Neurol. 1988;23 (Suppl):S143–S150. doi: 10.1002/ana.410230733. [DOI] [PubMed] [Google Scholar]
  30. Vallé A., Garrone P., Yssel H., Bonnefoy J. Y., Freedman A. S., Freeman G., Nadler L. M., Banchereau J. mAb 104, a new monoclonal antibody, recognizes the B7 antigen that is expressed on activated B cells and HTLV-1-transformed T cells. Immunology. 1990 Apr;69(4):531–535. [PMC free article] [PubMed] [Google Scholar]
  31. Weiss A., Wiskocil R. L., Stobo J. D. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level. J Immunol. 1984 Jul;133(1):123–128. [PubMed] [Google Scholar]
  32. Wucherpfennig K. W., Höllsberg P., Richardson J. H., Benjamin D., Hafler D. A. T-cell activation by autologous human T-cell leukemia virus type I-infected T-cell clones. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2110–2114. doi: 10.1073/pnas.89.6.2110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wyss-Coray T., Gallati H., Pracht I., Limat A., Mauri D., Frutig K., Pichler W. J. Antigen-presenting human T cells and antigen-presenting B cells induce a similar cytokine profile in specific T cell clones. Eur J Immunol. 1993 Dec;23(12):3350–3357. doi: 10.1002/eji.1830231243. [DOI] [PubMed] [Google Scholar]
  34. Yodoi J., Uchiyama T. Diseases associated with HTLV-I: virus, IL-2 receptor dysregulation and redox regulation. Immunol Today. 1992 Oct;13(10):405–411. doi: 10.1016/0167-5699(92)90091-K. [DOI] [PubMed] [Google Scholar]

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