PMID- 19709757 OWN - NLM STAT- MEDLINE DCOM- 20100416 LR - 20141120 IS - 1873-2534 (Electronic) IS - 0165-2427 (Linking) VI - 133 IP - 2-4 DP - 2010 Feb 15 TI - Induction of inducible CD4+CD25+Foxp3+ regulatory T lymphocytes by porcine reproductive and respiratory syndrome virus (PRRSV). PG - 170-82 LID - 10.1016/j.vetimm.2009.07.012 [doi] AB - Increases in numbers or activities of regulatory T lymphocytes (Tregs) have been linked to the establishments of several persistent infections. It has been previously shown that porcine reproductive and respiratory syndrome virus (PRRSV) can negatively modulate the host immune responses, resulting in persistent infection and secondary immunodeficiency. Recently, the existence of porcine CD4(+)CD25(+) Tregs has been demonstrated. We investigated the effect of PRRSV on the CD4(+)CD25(+) Tregs. The CD4(+)CD25(+)Foxp3(+) T lymphocytes in the peripheral blood mononuclear cells (PBMCs) were identified, using the anti-human anti-Foxp3 monoclonal antibody. In vitro culture of porcine PBMC in the presence of PRRSV, but not classical swine fever virus, significantly increased the numbers of Foxp3(+) lymphocytes, particularly in the CD4(+)CD25(high) subpopulation. The time-course study revealed that PRRSV significantly increased the numbers of viral-specific CD4(+)CD25(high)Foxp3(+) subpopulation in the culture starting from 12h through the end of the observation period. Consistent to the results obtained by flow cytometry, enhanced Foxp3 gene expression was observed in the PBMC cultured with PRRSV in a time-course manner. The presence of monocyte-derived DC in the co-culture significantly enhanced the induction of CD4(+)CD25(+) Foxp3(+) T lymphocytes. The PRRSV-induced CD4(+)CD25(high) T lymphocytes exhibited suppressive activity when co-cultured with PHA-activated, autologous peripheral blood leukocytes, indicating the suppressive activity of the PRRSV-specific Tregs. In addition, PRRSV exposure significantly increased the numbers of PRRSV-specific CD4(+)CD25(+)Foxp3(+) subpopulation in the PBMC of infected pigs at 10 days post-infection. In summary, the results indicated that PRRSV could increase the numbers of viral-specific, inducible regulatory T lymphocytes in the porcine PBMC, both in vitro and in vivo. The findings suggested the novel immunomodulatory mechanism induced by PRRSV. CI - Copyright 2009 Elsevier B.V. All rights reserved. FAU - Wongyanin, P AU - Wongyanin P AD - Interdisciplinary Program of Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand. FAU - Buranapraditkun, S AU - Buranapraditkun S FAU - Chokeshai-Usaha, K AU - Chokeshai-Usaha K FAU - Thanawonguwech, R AU - Thanawonguwech R FAU - Suradhat, S AU - Suradhat S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090803 PL - Netherlands TA - Vet Immunol Immunopathol JT - Veterinary immunology and immunopathology JID - 8002006 RN - 0 (Forkhead Transcription Factors) RN - 0 (Interleukin-2 Receptor alpha Subunit) SB - IM MH - Animals MH - Dendritic Cells/immunology MH - Forkhead Transcription Factors/genetics/metabolism MH - Gene Expression MH - In Vitro Techniques MH - Interleukin-2 Receptor alpha Subunit/metabolism MH - Lymphocyte Activation MH - Porcine Reproductive and Respiratory Syndrome/genetics/immunology MH - Porcine respiratory and reproductive syndrome virus/*immunology/pathogenicity MH - Sus scrofa/genetics/*immunology/*virology MH - Swine MH - T-Lymphocyte Subsets/immunology MH - T-Lymphocytes, Regulatory/*immunology MH - Time Factors EDAT- 2009/08/28 09:00 MHDA- 2010/04/17 06:00 CRDT- 2009/08/28 09:00 PHST- 2008/11/06 00:00 [received] PHST- 2009/07/01 00:00 [revised] PHST- 2009/07/28 00:00 [accepted] PHST- 2009/08/28 09:00 [entrez] PHST- 2009/08/28 09:00 [pubmed] PHST- 2010/04/17 06:00 [medline] AID - S0165-2427(09)00244-X [pii] AID - 10.1016/j.vetimm.2009.07.012 [doi] PST - ppublish SO - Vet Immunol Immunopathol. 2010 Feb 15;133(2-4):170-82. doi: 10.1016/j.vetimm.2009.07.012. Epub 2009 Aug 3.