Editing Macrophage (section)

==== Interactions with CD4<sup>+</sup> T Helper Cells ====
Macrophages are professional antigen presenting cells (APC), meaning they can present peptides from phagocytosed antigens on major histocompatibility complex (MHC) II molecules on their cell surface for T helper cells.<ref name="Guerriero-2019">{{cite journal | vauthors = Guerriero JL | title = Macrophages: Their Untold Story in T Cell Activation and Function | journal = International Review of Cell and Molecular Biology | volume = 342 | pages = 73–93 | date = 2019 | pmid = 30635094 | doi = 10.1016/bs.ircmb.2018.07.001 | publisher = Elsevier | isbn = 978-0-12-815381-9 }}</ref> Macrophages are not primary activators of naïve T helper cells that have never been previously activated since tissue resident macrophages do not travel to the lymph nodes where naïve T helper cells reside.<ref name="Itano-2003">{{cite journal | vauthors = Itano AA, Jenkins MK | title = Antigen presentation to naive CD4 T cells in the lymph node | journal = Nature Immunology | volume = 4 | issue = 8 | pages = 733–739 | date = August 2003 | pmid = 12888794 | doi = 10.1038/ni957 | s2cid = 10305140 }}</ref><ref name="Murphy-2016">{{Cite book | vauthors = Murphy K, Weaver C | title=Janeway's Immunobiology |publisher=Garland Science |year=2016 |isbn=978-0-8153-4505-3 |edition=9th |location=New York, New York |pages=363–364 |language=en}}</ref> Although macrophages are also found in secondary lymphoid organs like the lymph nodes, they do not reside in T cell zones and are not effective at activating naïve T helper cells.<ref name="Itano-2003" /> The macrophages in lymphoid tissues are more involved in ingesting antigens and preventing them from entering the blood, as well as taking up debris from apoptotic lymphocytes.<ref name="Itano-2003" /><ref name="Gray-2012">{{cite journal | vauthors = Gray EE, Cyster JG | title = Lymph node macrophages | journal = Journal of Innate Immunity | volume = 4 | issue = 5–6 | pages = 424–436 | date = 2012 | pmid = 22488251 | pmc = 3574571 | doi = 10.1159/000337007 }}</ref> Therefore, macrophages interact mostly with previously activated T helper cells that have left the lymph node and arrived at the site of infection or with tissue resident memory T cells.<ref name="Murphy-2016" />

Macrophages supply both signals required for T helper cell activation: 1) Macrophages present antigen peptide-bound MHC class II molecule to be recognized by the corresponding [[T-cell receptor|T cell receptor]] (TCR), and 2) recognition of pathogens by PRRs induce macrophages to upregulate the co-stimulatory molecules [[CD80]] and [[CD86]] (also known as [[B7 (protein)|B7]]) that binds to [[CD28]] on T helper cells to supply the co-stimulatory signal.<ref name="Murphy-2022"/><ref name="Guerriero-2019" /> These interactions allow T helper cells to achieve full effector function and provide T helper cells with continued survival and differentiation signals preventing them from undergoing apoptosis due to lack of TCR signaling.<ref name="Guerriero-2019" /> For example, [[Interleukin 2|IL-2]] signaling in T cells upregulates the expression of anti-apoptotic protein [[Bcl-2]], but T cell production of IL-2 and the high-affinity IL-2 receptor [[IL2RA|IL-2RA]] both require continued signal from TCR recognition of MHC-bound antigen.<ref name="Murphy-2022" /><ref>{{Cite journal | vauthors = Abbas AK |date=September 2020 |title=The Surprising Story of IL-2 |journal=The American Journal of Pathology |language=en |volume=190 |issue=9 |pages=1776–1781 |doi=10.1016/j.ajpath.2020.05.007|pmid=32828360 |s2cid=221280663 |doi-access=free }}</ref>