Regulation of CD4+ T-cell contraction during pathogen challenge
K Kai McKinstry, Tara M Strutt, Susan L Swain, K Kai McKinstry, Tara M Strutt, Susan L Swain
Abstract
Signals orchestrating productive CD4+ T-cell responses are well documented; however, the regulation of contraction of CD4+ T-cell effector populations following the resolution of primary immune responses is not well understood. While distinct mechanisms of T-cell death have been defined, the relative importance of discrete death pathways during the termination of immune responses in vivo remains unclear. Here, we review the current understanding of cell-intrinsic and -extrinsic variables that regulate contraction of CD4+ T-cell effector populations through multiple pathways that operate both initially during T-cell priming and later during the effector phase. We discuss the relative importance of antigen-dependent and -independent mechanisms of CD4+ T-cell contraction during in vivo responses, with a special emphasis on influenza virus infection. In this model, we highlight the roles of greater differentiation and presence in the lung of CD4+ effector T cells, as well as their polarization to particular T-helper subsets, in maximizing contraction. We also discuss the role of autocrine interleukin-2 in limiting the extent of contraction, and we point out that these same factors regulate contraction during secondary CD4+ T-cell responses.
Figures
![Fig. 1. T-cell contraction following influenza infection](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f1.jpg)
![Fig. 2. CD4 + T-cell contraction following…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f2.jpg)
![Fig. 3. Lung-resident effector CD4 + T…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f3.jpg)
![Fig. 4. Effector CD4 + T cells…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f4.jpg)
![Fig. 5. IFNγ does not appreciably impact…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f5.jpg)
![Fig. 6. Th-polarization impacts antigen-independent contraction of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f6.jpg)
![Fig. 7. In vitro contraction of Th1-polarized…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f7.jpg)
![Fig. 8. IL-2 regulates contraction of memory-effectors](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f8.jpg)
![Fig. 9. Signals impacting contraction of CD4…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2908916/bin/nihms212185f9.jpg)
Source: PubMed