THE ROLE OF HELPER T CELLS IN INFLAMMATORY RESPONSES
The understanding of the role of T lymphocytes in inflammation emerged with the study of a phenomenon known as delayed hypersensitivity . This abnormal immune reaction is manifest as a cutaneous reaction, often when a sensitized individual is chal-lenged by the introduction of a specific antigen into the skin. For example, the tuberculin test is a skin test designed to determine if an individual has been exposed to and has devel-oped hypersensitivity to antigenic products of Mycobacterium tuberculosis. A positive reaction to tuberculin is seen usually 24–48 hours after intradermal inoculation of the antigen and classified as a delayed hypersensitivity reaction. In contrast, patients allergic to pollens show a positive reaction to intradermally injected pollen extracts after a few minutes, a re-action termed immediate hypersensitivity.
Studies with experimental animals showed that it was possible to transfer cutaneous de-layed hypersensitivity reactions by transferring spleen cells from a sensitized animal to an MHC-identical nonimmune recipient. In this system, the cells primarily involved were CD4+ helper lymphocytes. Through the release of lymphokines active on lymphoid and nonlymphoid cells, the activated CD4+ cells led to the formation of a cellular infiltrate around the reactive area. The cellular infiltrate is usually rich in lymphocytes and mono-cytes reflecting the proliferation of activated CD4+ lymphocytes and the release of chemo-tactic factors that attracted monocytes to the area.
Granulomatous reactions are the expression of protracted T-cell activation in tissues, often caused by intracellular pathogens that have developed mechanisms of resistance to antimi- crobial defenses. The granulomas contain T lymphocytes, macrophages, histiocytes, and other cell types, often forming a barrier circumscribing a focus of infection. The formation of granulomas is due to the release of cytokines that attract and immobilize other mononu-clear cells. The activation of these cells in situ results in the release of enzymes that cause tissue destruction and cytokines that attract and activate additional inflammatory cells.
Graft rejection is also believed to be primarily mediated by activated CD4+ cells through the attraction and activation of inflammatory cells to the grafted organ.