CXCR4 EXPRESSION DURING LYMPHOPOIESIS - IMPLICATIONS FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF THE THYMUS

Human immunodeficiency virus type 1 (HIV-1) infection of the human thy mus results in depletion of CD4-bearing thymocytes. This depletion is initially manifested in the immature CD4(+)/CD8(+) thymocyte subset, T o determine cellular factors involved in HIV infection in the thymus. we examined the expression of the recently identified viral coreceptor , CXCR4. on fresh human thymocytes and on human cells from SCID-hu (Th y/Liv) mice, CXCR4 is a member of the chemokine receptor family which is required along with CD4 for entry into the cell of syncytium-induci ng (SI) HIV-1 strains, Our analyses show that CXCR4 expression is modu lated during T-lymphoid differentiation such that immature thymocytes display an increased frequency and higher surface density of the corec eptor than do more mature cells, In addition, using an SI strain of HI V-1 which directs expression of a reporter protein on the surface of i nfected cells, we have found that the immature CD4(+)/CD8(+) thymocyte s that express the highest levels of both CD4 and CXCR4 are the cells that are preferentially infected and depleted by the virus in vitro, T hus, high levels of both primary receptor and coreceptor may allow eff icient infection of the thymus by certain HIV-1 strains, This in part may explain the rapid disease progression seen in some HIV-infected ch ildren, where the thymus is actively involved in the production of new T lymphocytes.