RESEARCH HIGHLIGHTS NPG REGULATORY T CELLS TReg cells separate the weak from the strong Regulatory T (TReg) cells are known But how do TReg cells exert these observed in this model, the depletion for their role in peripheral tolerance effects? Intravital imaging of naive of TReg cells prior to the primary and are essential for preventing T cell receptor (TCR)-transgenic infection resulted in higher bacterial autoimmunity. But do they play a CD8+ T cells interacting with burdens during a secondary infection. part during active immune responses antigen-loaded dendritic cells (DCs) In addition, there were corresponding to foreign antigens? In a new study, in lymph nodes showed that the decreases in the number and relative Amigorena and colleagues dem- long-lasting interactions induced affinities of ovalbumin-specific CD8+ onstrate that TReg cells enhance the by a high-affinity antigen were T cells during the secondary response. + avidity of CD8 T cell responses to unaltered by TReg cell depletion. This suggests that the presence of foreign antigens and thereby improve By contrast, the shorter duration TReg cells during naive T cell priming T cell memory. T cell–DC contacts induced by a promotes the subsequent generation In initial experiments in mice, low-affinity antigen were extended in of functionally effective high-avidity + the authors showed that TReg cell the absence of TReg cells. This effect memory CD8 T cell responses. depletion during the priming stage could be reversed by the addition So, this study reveals an intrigu- + this of a CD8 T cell response to an of blocking antibodies specific for ing new role for TReg cells in the injected foreign antigen markedly mechanism CC-chemokine ligand 3 (CCL3), suppression of low-avidity CD8+ increased the numbers of antigen- could ... CCL4 and CCL5, suggesting that T cell responses to foreign antigens. specific CD8+ T cells in the spleen. T cells inhibit the production of As most autoreactive T cells in the explain how Reg Interestingly, however, the vast chemokines that stabilize low-affinity periphery have only low affinities majority of these T cells recognized TReg cells T cell–DC interactions. for self antigens, the authors propose the antigen with only low avidity, seemingly These findings were corroborated that this mechanism could also and thus the overall avidity of distinguish in an in vivo infection model using underlie the TReg cell-mediated sup- the response was reduced in the between ovalbumin-expressing Listeria mono- pression of these cells and may thus absence of T cells. By contrast, the cytogenes. Again, a lack of T cells at explain how T cells seemingly dis- Reg autoimmune Reg Reg depletion of TReg cells at later time the priming stage decreased the avid- tinguish between autoimmune and points affected only the propor- and foreign- ity of the ovalbumin-specific CD8+ foreign-antigen-specific responses. tion of antigen-specific T cells and antigen- T cell response. This was associated Isabel Woodman not their avidity. This implies that with a reduction in T cell interferon-γ specific TReg cells might function during the production and a rise in the produc- ORIGINAL RESEARCH PAPER Pace, L. et al. priming of CD8+ T cells to suppress responses tion of CCL2, CCL3 and CCL4 in the Regulatory T cells increase the avidity of primary low-avidity responses to foreign spleen. Although no impact on the CD8+ T cell responses and promote memory. Science 338, 532–536 (2012) antigens. clearance of the primary infection was NATURE REVIEWS | IMMUNOLOGY VOLUME 12 | DECEMBER 2012 © 2012 Macmillan Publishers Limited. All rights reserved.