Spontaneous Cell Proliferation is Associated with Poor Sensitivity to Glucocorticoids in Patients Infected with HTLV

Overview

Journal Cell Prolif

Date 2007 Jan 18

PMID 17227296

Citations 1

Authors

R P Lopes

M Menna-Barreto

M E Bauer

Affiliations

Soon will be listed here.

Abstract

Background: Human T-cell lymphotropic viruses (HTLV)-I/II have a special tropism for infecting T cells and inducing spontaneous lymphocyte proliferation. Leukaemia and neurological manifestations are associated with HTLV-I/II infections, and treatment is usually based on anti-inflammatory drugs including glucocorticoids. Although steroid resistance has been reported, it is unknown whether this condition is related to the infection itself or to the treatment.

Objective: We investigated whether spontaneous cell proliferation is associated with T-cell sensitivity to glucocorticoids.

Materials And Methods: Twenty-eight HTLV-I/II patients and 11 healthy age-matched controls took part in this study. Lymphocytes were isolated and cultured in vitro to measure spontaneous and mitogen-induced proliferation as well as cellular sensitivity to dexamethasone.

Results: Patients with HTLV-I/II infection showed similar stimulated and unstimulated T-cell proliferation as well as comparable sensitivity to dexamethasone in vitro. There were no group differences in the frequency of glucocorticoid responders versus non-responders. However, T cells of patients with spontaneous proliferation were unresponsive to mitogenic stimulation and were remarkably more resistant to dexamethasone than cells of patients with normal proliferation.

Conclusion: These data suggest that the poor clinical response to steroids may be associated with spontaneous cell proliferation during HTLV infection.

Citing Articles

Glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia is associated with a proliferative metabolism.

Beesley A, Firth M, Ford J, Weller R, Freitas J, Perera K Br J Cancer. 2009; 100(12):1926-36.

PMID: 19436302 PMC: 2714233. DOI: 10.1038/sj.bjc.6605072.

References

Nakagawa M, Nakahara K, Maruyama Y, Kawabata M, Higuchi I, Kubota H . Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis. J Neurovirol. 1996; 2(5):345-55. DOI: 10.3109/13550289609146899. View

Cartier L, Cea J, Vergara C, Araya F, Born P . Clinical and neuropathological study of six patients with spastic paraparesis associated with HTLV-I: an axomyelinic degeneration of the central nervous system. J Neuropathol Exp Neurol. 1997; 56(4):403-13. DOI: 10.1097/00005072-199704000-00009. View

PRINCE H, Golding J, York J . Lymphocyte subset alterations associated with increased spontaneous lymphocyte proliferation in human T lymphotropic virus (HTLV) infection: distinctive patterns for HTLV-I versus HTLV-II infection. J Infect Dis. 1994; 169(6):1409-10. DOI: 10.1093/infdis/169.6.1409. View

Murphy E, Blattner W . HTLV-I-associated leukemia: a model for chronic retroviral diseases. Ann Neurol. 1988; 23 Suppl:S174-80. DOI: 10.1002/ana.410230739. View

PRINCE H, Swanson P . Spontaneous lymphocyte proliferation in human T lymphotropic virus type II infection is associated with increased provirus load. J Infect Dis. 1993; 168(6):1599-600. DOI: 10.1093/infdis/168.6.1599. View

Hollsberg P . Pathogenesis of chronic progressive myelopathy associated with human T-cell lymphotropic virus type I. Acta Neurol Scand Suppl. 1997; 169:86-93. DOI: 10.1111/j.1600-0404.1997.tb08156.x. View

Uchiyama T . Adult T-cell leukemia. Blood Rev. 1988; 2(4):232-8. DOI: 10.1016/0268-960x(88)90012-4. View

Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A . HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986; 1(8488):1031-2. DOI: 10.1016/s0140-6736(86)91298-5. View

Mann D, MARTIN P, Nalewaik R, Blattner W . Virus production and spontaneous cell proliferation in HTLV-I-infected lymphocytes. Clin Immunol Immunopathol. 1994; 72(3):312-20. DOI: 10.1006/clin.1994.1147. View

10.

Maloney E, Biggar R, Neel J, Taylor M, Hahn B, Shaw G . Endemic human T cell lymphotropic virus type II infection among isolated Brazilian Amerindians. J Infect Dis. 1992; 166(1):100-7. DOI: 10.1093/infdis/166.1.100. View

11.

Franchini G . Molecular mechanisms of human T-cell leukemia/lymphotropic virus type I infection. Blood. 1995; 86(10):3619-39. View

12.

Matsushita K, Arima N, Ohtsubo H, Fujiwara H, Arimura K, Kukita T . Poor response to prednisolone of idiopathic thrombocytopenia with human T-lymphotropic virus type I infection. Am J Hematol. 2002; 71(1):20-3. DOI: 10.1002/ajh.10173. View

13.

Khabbaz R, Hartel D, Lairmore M, Horsburgh C, Schoenbaum E, Roberts B . Human T lymphotropic virus type II (HTLV-II) infection in a cohort of New York intravenous drug users: an old infection?. J Infect Dis. 1991; 163(2):252-6. DOI: 10.1093/infdis/163.2.252. View

14.

Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H . Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977; 50(3):481-92. View

15.

Heneine W, Kaplan J, Gracia F, Lal R, Roberts B, Levine P . HTLV-II endemicity among Guaymi Indians in Panama. N Engl J Med. 1991; 324(8):565. DOI: 10.1056/NEJM199102213240815. View

16.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

17.

Gessain A, Barin F, Vernant J, Gout O, Maurs L, Calender A . Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985; 2(8452):407-10. DOI: 10.1016/s0140-6736(85)92734-5. View

18.

Piccardo P, Ceroni M, Rodgers-Johnson P, Mora C, Asher D, Char G . Pathological and immunological observations on tropical spastic paraparesis in patients from Jamaica. Ann Neurol. 1988; 23 Suppl:S156-60. DOI: 10.1002/ana.410230735. View

19.

Umehara F, Abe M, Koreeda Y, Izumo S, Osame M . Axonal damage revealed by accumulation of beta-amyloid precursor protein in HTLV-I-associated myelopathy. J Neurol Sci. 2000; 176(2):95-101. DOI: 10.1016/s0022-510x(00)00324-5. View

20.

Zanetti A, Galli C . Seroprevalence of HTLV-I and HTLV-II. N Engl J Med. 1992; 326(26):1783; author reply 1783-4. View