New T-lymphocytic cell lines for studying cell infectability by human immunodeficiency virus

We identified five human T-lymphoid cell lines (PB-1, Sez-4, C19PL, HUT 102 B and ATL-2) which highly express CD4 in addition to CXCR4 and CCR5. In ord er to evaluate if these cells are infectabile by human immunodeficiency vir us (HIV) and could be employed as a model in HIV research we exposed these cell lines to X4 (T-cell tropic) and R5 (macrophage tropic) and subsequentl y tried to correlate their infectability with (i) level of chemokine corece ptor (CXCR4 and CCR5) expression, (ii) coreceptor functionality (calcium fl ux, chemotaxis and phosphorylation of MAPK p42/44 and AKT) and (iii) endoge nous expression and secretion of HIV-related chemokines which compete with the virus for binding to CXCR4 (SDF-1/CXCL12) or CCR5 (MIP-1 beta /CCL4, MI P-1 alpha /CCL3, RANTES/CCL5, MCP-2/CCL8, MCP-3/CCL7 and MCP-4/CCL13). We d emonstrated that while PB-1 cells are infectable by both X4 and R5 HIV, Sez -4, C91PL,HUT 102B and ATL-2 cells were infected by X4 HIV only. Moreover, we noticed that the susceptibility of these cells to HIV did not correspond either with the level of surface expression or with the functionality of C XCR4 or CCR5; however, it was modulated to some degree by the endogenously secreted HIV-related chemokines. Thus all five mature T-cell lines describe d here may provide useful new models for studying various aspects of HIV in fection. In addition we demonstrate that the infectability of cells by HIV is modulated by so far unidentified intrinsic factors as well as some alrea dy known endogenously secreted chemokines. The identification of these: fac tors may be important for developing new strategies to protect cells from H IV infection.