IL-2-Independent and TNF- alpha -Dependent Expansion of V beta 5+ Natural Regulatory T Cells during Retrovirus Infection

• Published in: The Journal of immunology (1950) Vol. 190; no. 11; pp. 5485 - 5495
• Main Authors: Myers, Lara, Joedicke, Jara J, Carmody, Aaron B, Messer, Ronald J, Kassiotis, George, Dudley, Jaquelin P, Dittmer, Ulf, Hasenkrug, Kim J
• Format: Journal Article
• Language: English
• Published: 01.06.2013
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.1202951

Friend virus infection of mice induces the expansion and activation of regulatory T cells (Tregs) that dampen acute immune responses and promote the establishment and maintenance of chronic infection. Adoptive transfer experiments and the expression of neuropilin-1 indicate that these cells are predominantly natural Tregs rather than virus-specific conventional CD4+ T cells that converted into induced Tregs. Analysis of Treg TCR V beta chain usage revealed a broadly distributed polyclonal response with a high proportionate expansion of the V beta 5+ Treg subset, which is known to be responsive to endogenous retrovirus-encoded superantigens. In contrast to the major population of Tregs, the V beta 5+ subset expressed markers of terminally differentiated effector cells, and their expansion was associated with the level of the antiviral CD8+ T cell response rather than the level of Friend virus infection. Surprisingly, the expansion and accumulation of the V beta 5+ Tregs was IL-2 independent but dependent on TNF- alpha . These experiments reveal a subset-specific Treg induction by a new pathway.