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Title: Rapid and transient activation of gamma/delta T cells to interferon gamma production, NK cell-like killing and antigen processing during acute virus infection

Author
item TOKA, FELIX - Warsaw University Of Life Sciences
item Kenney, Mary
item Golde, William

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/10/2011
Publication Date: 4/15/2011
Citation: Toka, F.N., Kenney, M.A., Golde, W.T. 2011. Rapid and transient activation of gamma/delta T cells to interferon gamma production, NK cell-like killing and antigen processing during acute virus infection. Journal of Immunology. 186(8):4853-4861.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) infection of cattle and swine is a highly acute infection. Disease is expressed within a few days of exposure, infected animals shed large amounts of virus spreading the infection through a herd or premises, and virus is cleared from the individual quickly, followed by resolution of disease symptoms. Different early immune responses, specific and nonspecific, combine to mediate rapid elimination of the virus. These responses are potential targets of rapid acting vaccines. Here we show results of analysis of a prominent population of lymphocytes in the circulation of ruminants, the gamma/delta T cells, during infection of cattle with FMDV. The data presented show that this cell population is rapidly activated to multiple functions that are involved in combating the viral infection. Remarkably, these activated cells detected within 72 hours of infection with the virus but was no longer found in the blood 5 days after infection. These cells appear to mediate a rapid and highly transient antiviral response and may play a role in early immunity to FMDV. Therefore, vaccines that target gamma/delta T cell activation have the potential to provide rapid protection against FMDV infection.

Technical Abstract: Gamma/delta T cells are the majority peripheral blood T cells in young cattle. The role of gamma/delta T cells in innate responses against infection with foot-and-mouth disease virus (FMDV) was analyzed on 5 consecutive days following infection. Before infection, bovine gamma/delta T cells expressed a non-activated phenotype relative to CD62L, CD45RO and CD25 expression and did not produce IFN gamma ex vivo. Additionally, CD335 expression was lacking on gamma/delta T cells and no spontaneous target cell lysis could be detected in vitro, although perforin was detectable at a very low level. MHC Class II and CD13 expression were also lacking. Following infection with FMDV, expression of CD62L and CD45RO was greatly reduced on gamma/delta T cells and unexpectedly, CD45RO expression did not recover. A transient increase in expression of CD25 correlated with production of IFN gamma. Expression of CD335 and production of perforin was detected on a subset of gamma/delta T cells and this correlated with an increased spontaneous killing of xenogeneic target cells. Further, increased MHC class II expression was detected on gamma/delta T cells and these cells processed protein antigens. These activities are rapidly induced, within 3 days, and wane by 5 days following infection. All of these functions, NK-like killing, antigen processing and IFN gamma production, have been demonstrated for these cells in various species. However, these results are unique in that all these functions are detected in the same samples of gamma/delta T cells suggesting a pivotal role of these cells in controlling virus infection.