Recommended Readings: Susan Kaech, Ph.D., September 14th

Monday Lecture Series
Monday, September 14th, 2015
4:00 p.m., Carson Family Auditorium (CRC)

Susan Kaech, Ph.D.
Associate Professor of Immunobiology,
Yale School of Medicine
Early Career Scientist,
Howard Hughes Medical Institute

PEPing Up T Cell-mediated Immunity to Viruses and Cancer

Recommended Readings

Empirical Articles

Cui, G., Staron, M. M., Gray, S. M., Ho, P. C., Amezquita, R. A., Wu, J., & Kaech, S. M. (2015). IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell, 161(4), 750-761. doi:10.1016/j.cell.2015.03.021.

Laidlaw, B. J., Cui, W., Amezquita, R. A., Gray, S. M., Guan, T., Lu, Y., … & Kaech, S. M. (2015). Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells. Nature Immunology, 16(8), 871-879. doi:10.1038/ni.3224

Laidlaw, B. J., Zhang, N., Marshall, H. D., Staron, M. M., Guan, T., Hu, Y., … & Kaech, S. M. (2014). CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection. Immunity, 41(4), 633-645. doi:10.1016/j.immuni.2014.09.007.

Slütter, B., Pewe, L. L., Kaech, S. M., & Harty, J. T. (2013). Lung airway-surveilling CXCR3 hi memory CD8+ T cells are critical for protection against influenza A virus. Immunity, 39(5), 939-948. doi:10.1016/j.immuni.2013.09.013.

Review Paper

Gray, S. M., Kaech, S. M., & Staron, M. M. (2014). The interface between transcriptional and epigenetic control of effector and memory CD8+ T‐cell differentiation. Immunological Reviews, 261(1), 157-168. doi:10.1111/imr.12205.

Kaech, S. M., & Cui, W. (2012). Transcriptional control of effector and memory CD8+ T cell differentiation. Nature Reviews Immunology, 12(11), 749-761. doi:10.1038/nri3307.

Mild Fever Enhances Effectiveness of CD8+ T-cells

Scientists have found that the generation and differentiation of CD8+ cytotoxic T-cell is enhanced by mild fever-range hyperthermia. Specifically, their research suggests that elevated body temperature changes the T-cells’ membranes which may help mediate the effects of micro-environmental temperature on cell function. To test this, researchers injected two groups of mice with an antigen, and examined the activation of T-cells following the interaction with antigen presenting cells. Body temperature in half of the mice was raised by 2 degrees centigrade, while the other half maintained a normal core body temperature. In the warmed mice, results showed a greater number of the type of CD8 T-cells capable of destroying infected cells. Read more in the Journal of Leukocyte Biology.

Enhanced expression of T-cell receptors in CD8 T cells increases HIV-1 binding 450-fold

Investigators at the University of Pennsylvania School of Medicine and Cardiff University, UK have engineered T-cells which are able to recognize HIV-1 strains that typically fall under the radar.  In the November 9, 2008 advanced online Nature Medicine publication of Control of HIV-1 immune espcape by CD8 T cells expressing enhanced T-cell receptor, researchers describe T cells that bonded more strongly and in a more aggressive manner so that fewer T cells were required to control HIV-1 infection.

It is hoped that clinical trials with the engineered T-cells will begin in 2009 to establish safety.  If laboratory results can be translated effectively in the clinic, a powerful “disguise detection” therapy may emerge which could treat early-stage HIV-1 infections. 

(Extracts from ScienceDaily, November 10, 2008 and Nature Medicine published online November 9, 2008; doi:10.1038/nm.1779)