HUMAN T-CELL LEUKEMIA-VIRUS TYPE-II DIRECTLY ACTS ON CD34(- ENVELOPE-ASSOCIATED HLA CLASS-II MOLECULES REVERSE THIS EFFECT() HEMATOPOIETIC PRECURSORS BY INCREASING THEIR SURVIVAL POTENTIAL )

The role of human T-cell leukemia virus type II (HTLV-II) in human lym phoproliferative and hematopoietic abnormalities in which the retrovir us can be isolated is still elusive. Here we show that the C344 T-cell -derived lymphotropic HTLV-II type IIa Mo strain acts directly on CD34 (+) hematopoietic precursors by rescuing them from apoptosis induced b y interleukin-1 (IL-3) deprivation. This effect is viral strain-specif ic, as it is not observed with the B-lymphotropic HTLV-II type IIb Gu strain, it does not require infection of the hematopoietic precursors, and, interestingly, it is strongly dependent on the infected cellular host from which the virus was derived. Indeed, growth adaptation of t he Mo strain to the permissive B-cell line, BJAB, renders the virus no longer capable of mediating the antiapoptotic effect, However, pretre atment of the BJAB-adapted Mo strain with antibodies specific for HLA class II, but not class I, histocompatibility antigens restores the an tiapoptotic potential of the virus, These results constitute the first evidence that HTLV-II retrovirus can directly influence the homeostas is of human pro genitors, without infecting them, and that this crucia l activity is strongly inhibited by the presence of host-derived envel ope-associated HLA class II antigens. (C) 1998 by The American Society of Hematology.