Rabi Upadhyay
medical student
University of Massachusetts

Kieran, MA, US

For how long do macrophages dock with helper T cells?

Rabi Upadhyay
HHMI medical fellow,
medical student,
Medical School,
University of Massachusetts
The short answer: The exact interaction time between macrophages and helper T cells is still debated. It's assumed to be very short (i.e., 1–2 seconds) in the vast majority of cases, but when there is a cognate antigen interaction it's hypothesized to range from 0 to 5 minutes up to more than 15 minutes (some would even surmise long-term interactions measured in hours but that has never been shown).

More detail: Initial work examining this question in vitro is difficult to uphold now that we appreciate the vast complexity of interactions in vivo. In pursuing a rigorous answer, the best tool has been intravital multiphoton microscopy. Scientists can fluorescently "tag" different cell populations and try to follow them as long as they stay within a shallow volume (limited by the optical physics of microscopy).

The only definitive experiment would be to visualize the actual docking of a macrophage and a CD4 lymphocyte, but clearly that is a very difficult event to make happen at a prearranged, predictable tissue location and time frame. Researchers have had some success in elucidating the physical interactions between T cells and dendritic cells specifically in lymph nodes, and it's reasonable to assume that they are comparable interactions. You can surgically expose and immobilize a particular lymph node in a mouse, and this volume of tissue can be imaged serially in time—essentially creating "movies" of cell populations swimming around the organ. Such work has revealed that naive T cells in lymph nodes of anesthetized mice continuously migrate and scan antigen-presenting dendritic cell populations. These (and other) results have helped to explain how lymphocytes optimize their chances of encountering rare cognate antigens and initiate adaptive immune responses.

Scientists have also made some inroads while examining the interactions of macrophages and tumors. This experiment is possible since large tumors (a few millimeters in diameter) can be grown in mice and this predefined volume can be immobilized under a microscope. T cells in the tumor stroma are shown to form long-lasting interactions with tumor-associated monocytes/macrophages (TAMs), which suggests cognate interactions. However, since monocytes/macrophages are functionally heterogeneous, it is important going forward to determine how different subtypes of TAMs are affected by their interaction with tumor-infiltrating lymphocytes in vivo.

Again, this information does not specifically define cognate interaction times between macrophages and helper T cells, but the tumor macrophage data and B-cell–T-cell interaction data do provide some insight.

For some experimental data see:

Thorsten R., et al. 2006 Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation. Immunity. 25, 129-141. doi:10.1016/j.immuni.2006.04.015

Okada T, Miller MJ, Parker I, Krummel MF, Neighbors M, et al. 2005 Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells. PLoS Biol 3(6): e150. doi:10.1371/journal.pbio.0030150

For further reviews and original research results, the following papers are especially informative:

Pittet MJ, Weissleder R. 2011 Intravital imaging. Cell. 147(5):983–91.

Pittet MJ, Mempel TR. 2008 Regulation of T-cell migration and effector functions: insights from in vivo imaging studies. Immunol Rev. 221:107–29.

Mrass P, et al. 2006 Random migration precedes stable target cell interactions of tumor-infiltrating T cells. J Exp Med. 203(12): 2749–2761. doi: 10.1084/jem.20060710.

10/23/11 14:43