HIV type 1-reactive chemokine-producing CD8+ and CD4+ cells expanded from infected lymph nodes.
The chemokines RANTES, MIP-1alpha, and MIP-1beta 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/microl 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/microl in their peripheral blood. Expanded cells were a mixture of CD8+CD45RO+ and 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-1alpha 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.
Triozzi
P L
PL
The Arthur G. James Cancer Hospital and Research Institute, The Ohio State University, Columbus 43210, USA.
Bresler
H S
HS
Aldrich
W A
WA
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D016853:Muromonab-CD3; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012333:RNA, Messenger / Q000032:analysis; D014779:Virus Replication
D018925:Chemokines; D007376:Interleukin-2; D016853:Muromonab-CD3; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1