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Induction of V gamma 2 V delta 2 T cell proliferation by activated antigen-specific CD4+ T cells and IL-2
J Burns1, B Bartholomew, S Lobo
1Department of Neurology, Veterans Administration Medical Center, University of Utah School of Medicine, Salt Lake City 84148, USA.
Human gamma delta T cells respond to a wide range of ligands including some T lymphocyte cellular antigens associated with viral infection. In the present study we examined the participation of gamma delta T cells in the proliferative response that is induced in human peripheral blood mononuclear cells (PBMC) by activated, antigen-reactive, CD4+ T cells. Activated, irradiated, myelin basic protein (MBP)-specific T cells stimulate brisk proliferation when cultured with freshly isolated, autologous PBMC. Determination of the phenotype of the responding PBMC T cells revealed a prominent expansion of gamma delta T cells, principally of the V gamma 2 subset. There was only minimal proliferation of PBMC following culture with irradiated, MBP-specific T cells that had not been recently activated. However, addition of rIL-2 to cultures of PBMC and nonstimulated MBP-specific T cells restored proliferation and the expansion of the gamma delta T cells. IL-2 alone did not mediate this effect. While MBP was a convenient antigen to use in these experiments, similar gamma delta T cell expansion in vitro was noted using activated, CD4+ T cells reactive with an exogenous antigen, Candida. In additional experiments, gamma delta-enriched T cell lines and certain V gamma 2 T cell clones continued to respond to activated but not to nonstimulated, CD4+ T cells. Overall, this study suggests that V gamma 2 V delta 2 T cells may proliferate as a consequence of the activation of CD4+ T cells. At least one ligand associated with T cell activation is required in addition to IL-2.
Human gamma delta T cells respond to a wide range of ligands including some T lymphocyte cellular antigens associated with viral infection. In the present study we examined the participation of gamma delta T cells in the proliferative response that is induced in human peripheral blood mononuclear cells (PBMC) by activated, antigen-reactive, CD4+ T cells. Activated, irradiated, myelin basic protein (MBP)-specific T cells stimulate brisk proliferation when cultured with freshly isolated, autologous PBMC. Determination of the phenotype of the responding PBMC T cells revealed a prominent expansion of gamma delta T cells, principally of the V gamma 2 subset. There was only minimal proliferation of PBMC following culture with irradiated, MBP-specific T cells that had not been recently activated. However, addition of rIL-2 to cultures of PBMC and nonstimulated MBP-specific T cells restored proliferation and the expansion of the gamma delta T cells. IL-2 alone did not mediate this effect. While MBP was a convenient antigen to use in these experiments, similar gamma delta T cell expansion in vitro was noted using activated, CD4+ T cells reactive with an exogenous antigen, Candida. In additional experiments, gamma delta-enriched T cell lines and certain V gamma 2 T cell clones continued to respond to activated but not to nonstimulated, CD4+ T cells. Overall, this study suggests that V gamma 2 V delta 2 T cells may proliferate as a consequence of the activation of CD4+ T cells. At least one ligand associated with T cell activation is required in addition to IL-2.