HAM/TSP : rendez-vous of Thy1, CD7 antigens and HTLV-1 gag protein ?

YP Plumelle, PhD

University hospital Center of Fort de France, Fort de France, Martinique, France

Certain HLA antigens predispose to HTLV-1 infection. Others predispose more specifically to he pathologies of ATL or HAM/TSP. HTLV-1 favors clonal expansion as a mode of replication. The phenotype of ATL cells is CD4+CD25+CD7low. The depletion of CD7 antigen alters the TCR/CD3 activation pathway, and HTLV-1 favors the CD2/LFA3 pathway. The T-CD4/CD7- subsets secretes TGF-1, antitumoral and antiinflammatory cytokine, which increases the proliferation of CD7 clones. Strongyloïdes stercoralis (Ss), hypothetical cofactor of the leukemogenesis initiated by HTLV-1, induces the expansion of specific T-CD4/CD7- clones. Certain of these clones may have tumoral potential. Autoimmune symptoms are rare in the course of ATL. HAM/TSP, on the other hand, manifests as an autoimmune disease, and clonal expansion evolves in another manner. By privileging the expansion of proinflammatory Th1 clones, HTLV-1, via the protein tax, induces the activation of LFA-1/ICAM-1 pathway. This activated pathway sets off the transcription of the HTLV-1-gag gene on the infected cells. The expression of the CD7 antigen is not diminished. In other aspects, the apoptosis of the cells of the CNS play a role in the pathogenesis of HAM/TSP. The CD3/TCR complex and Thy1 antigen works synergetically to the induce fragmentation of ADN and cellular growth arrest. Finally, the interaction of Thy-1 with the astrocytes can suppress axonal regeneration after CNS lesion. An homology of sequences exists between the genes CD7 and Thy-1. Thy-1, thymic antigen, is manifested in the CNS. The waves of T-CD4+CD7+ infected by HTLV-1 manifest protein gag. Could HAM/TSP be at the crossroads of the paths of the tree antigens CD7, Thy-1 and HTLV-1 gag ?

KEY WORDS: autoimmune, clonal expansion.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Autoimmunity.