Interleukin-2 stimulated T cell receptor V gamma 3 positive thymocytes do not migrate to the skin.
T cell receptor (TcR) V gamma 3+ thymocytes, which only develop in the fetal thymus, migrate to the skin. IL-2 stimulation of fetal day 18 murine thymocytes results in a cell population of which 45% of the cells express the TcR V gamma 3. In this study, we describe that those IL-2 cultured TcR V gamma 3+ thymocytes have the killing capacity of lymphokine activated killer cells: NK-susceptible as well as NK-resistant tumor cell lines were killed in an MHC-unrestricted manner. Because of these findings, IL-2-expanded TcR V gamma 3+ thymocytes could have a potential use in adoptive immunotherapy for skin-located tumors. Therefore, we analyzed the migration pattern of IL-2-cultured TcR V gamma 3+ thymocytes upon i.v. injection. We describe their initial entrapment in the lungs and subsequent accumulation in the liver. Localization in the skin was practically absent, and did not differ from that of IL-2 cultured adult thymocytes (mainly TcR alpha beta +). The migration pattern was identical in adult and newborn normal mice, and in adult nude mice. Analysis of the expression of asialo-GM1 revealed that it increased strongly after IL-2 culture. The relevance of this change in asialo-GM1 expression with reference to the migration upon i.v. injection is discussed. This study indicates that an improved understanding of the determinants of in vivo localization of IL-2 cultured cells may lead to improved strategies for adoptive immunotherapy of cancer.
Leclercq
G
G
Laboratory of Bacteriology, Virology and Immunology, University of Ghent, Belgium.
De Smedt
M
M
Plum
J
J
D000367:Age Factors; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D014018:Tissue Distribution
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins