HIV type 1-reactive chemokine-producing CD8+ and CD4+ cells expanded from infected lymph nodes

The chemokines RANTES, MIP-1 alpha, and MIP-1 beta have been identified as HIV-1-suppressive factors produced by CD8(+) T cells, We examined the possibility that HIV-1-specific, chemokine-releasing T cells could be expanded from the lymph nodes of patients with advanced infection. Lymphocytes, separated from lymph nodes of patients with peripheral blood CD4 counts less than 500/mu l obtained at diagnostic biopsies, were activated with anti-CD3 monoclonal antibody, and cultured in vitro for up to 12 days with IL-2, The phenotype, proliferative response, chemokine production, and anti-HIV-1 activity of the expanded cells was examined. Cells expanded 2,4- to 49-fold from patients with as few as 15 CD4(+) cells/mu l in their peripheral blood, Expanded cells were a mixture of CD8(+)CD45RO(+) acid CD4(+)CD45RO(+) T cells, The CD8(+) cells were also CD30(+)CDw60(+)CD11b(-). When challenged with autologous B cell targets expressing HIV-1 Env protein, unseparated expanded cells, and purified CD8(+) and CD4(+) T cell subsets, proliferated and secreted MIP-1 alpha and RANTES, Expanded cells were negative for HIV-1 by PCR and by culture, Culture supernatants inhibited the replication of HIV-1 in CD4(+) cells in vitro, These studies indicate that HIV-1 can stimulate chemokine release by CD8(+) and CD4(+) cells expanded from infected lymph nodes, even from individuals with advanced infection. The numbers of chemokine-releasing T cells produced in these short-term cultures may be sufficient to be applied therapeutically as an autologous cellular therapy for HIV-1.