Activation of C-C beta-chemokines in human peripheral blood gamma delta T cells by isopentenyl pyrophosphate and regulation by cytokines

Human gamma delta T lymphocytes respond to viral, bacterial, protozoal, and tumoral antigens, but their precise function remains unknown. In adults th e major circulating gamma delta T-cell subset expresses the V gamma 9V delt a 2 T-cell receptor and responds to protease-resistant phosphorylated deriv atives found in many pathogens. In this study we show that activation of V delta 2(+) cells with the nonpeptidic antigen isopentenyl pyrophosphate (IP P) rapidly induces (within 4-12 hours) the C-C chemokines MIP-1 alpha, MIP- 1 beta, and lymphotactin but not MCP-1,The most robust response was obtaine d for MIP-1 beta, IPP induction of MIP-1 alpha and MIP-1 beta was not affec ted by costimulation with interleukin-4 (IL-4), IL-10, TGF-beta, or interfe ron-gamma (INF-gamma). However, IL-12 significantly enhanced IPP-induced ex pression and release of MIP-1 alpha that was down-regulated by IGF-beta whe reas the induction of MIP-1 beta by IPP+IL-12 was refractory to cotreatment with TGF beta indicating that these chemokines are differentially regulate d by these cytokines. V delta 2(+) T cells also expressed a wide range of C -C chemokine receptors including CCR1, CCR5, and CCR8, all of which were do wn-regulated following activation. We conclude that V delta 2(+) cells can be rapidly induced by components of bacterial cell walls to express high le vels of proinflammatory chemokines, supporting an important role for these cells in the early stages of the inflammatory responses to many common path ogens. (C) 2000 by The American Society of Hematology.