L T Araújo Janahú1,2, Carlos Araujo Da Costa3, Antonio Carlos Rosário Vallinoto3, Barbara Brasil Santana3, Jessica Ribeiro-Lima1, Joanna Reis Santos-Oliveira1,4,5, Thaize Quiroga Chometon6, Alvaro Luis Bertho7, Wilson Savino8,5, Alda Maria Da-Cruz1,5, Adriano Gomes-Silva9. 1. Interdisciplinary Laboratory of Medical Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 2. Nucleus of Tropical Medicine, Federal University of Pará, Belém, Brazil. 3. Laboratory of Virology, Federal University of Pará, Belém, Brazil. 4. Nucleus of Applied Biomedical Sciences, Federal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, Brazil. 5. National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 6. Flow Cytometry Core Facility, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 7. Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 8. Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 9. Clinical Research Laboratory on Mycobacteria, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, adriano.gomes@ini.fiocruz.br.
Abstract
INTRODUCTION: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy associated with an inflammation of the central nervous system (CNS), being characterized by perivascular infiltration of inflammatory cells. HTLV-1-infected cells have the capacity to migrate through endothelial layers by enhancing adhesion receptor expression and corresponding ligands. T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cell migration and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. METHODS: Herein we studied the expression of 3 integrin alpha chains (CD49d, CD49e, and CD49f) on the membrane of T-cell subsets in patients infected by HTLV-1, both HAM/TSP patients and oligo/asymptomatic subjects who were asymptomatic or presented slight manifestations related to the virus infection. RESULTS: We observed higher peripheral blood frequency of CD49dhiCD4+ and CD49dhiCD8+ T cells in HTLV-1-infected patients. CONCLUSION: Our findings suggest that the increased expression of adhesion molecules, such as CD49d on T lymphocytes from HTLV-1-infected patients may contribute to the pathogenesis of the disease, in both oligo/asymptomatic and HAM/TSP-infected subjects. Accordingly, it is conceivable that there is a potential use of CD49d as target for a therapeutic approach aiming at blocking migration of activated T cells from HTLV-1-infected patients into the CNS, thus avoiding the progression to HAM/TSP.
INTRODUCTION:HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy associated with an inflammation of the central nervous system (CNS), being characterized by perivascular infiltration of inflammatory cells. HTLV-1-infected cells have the capacity to migrate through endothelial layers by enhancing adhesion receptor expression and corresponding ligands. T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cell migration and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. METHODS: Herein we studied the expression of 3 integrin alpha chains (CD49d, CD49e, and CD49f) on the membrane of T-cell subsets in patientsinfected by HTLV-1, both HAM/TSPpatients and oligo/asymptomatic subjects who were asymptomatic or presented slight manifestations related to the virus infection. RESULTS: We observed higher peripheral blood frequency of CD49dhiCD4+ and CD49dhiCD8+ T cells in HTLV-1-infectedpatients. CONCLUSION: Our findings suggest that the increased expression of adhesion molecules, such as CD49d on T lymphocytes from HTLV-1-infectedpatients may contribute to the pathogenesis of the disease, in both oligo/asymptomatic and HAM/TSP-infected subjects. Accordingly, it is conceivable that there is a potential use of CD49d as target for a therapeutic approach aiming at blocking migration of activated T cells from HTLV-1-infectedpatients into the CNS, thus avoiding the progression to HAM/TSP.