Macrophages can regulate lymphocyte proliferation and differentiation by various mechanisms, some of which are under the control of the MHC gene complex. Three distinct functions of the macrophage can be identified: 1) antigen presentation; 2) stimulation or inhibition of lymphocyte proliferation, resulting from secretion of mitogens or inhibitors; this function is modulated by phagocytosis of antigen, interaction with lymphocytes, and the state of macrophage activation; and 3) control of antigen-independent differentiation, as it takes place, for example, during part of thymocyte maturation.

Antigen presentation can be regulated by the MHC gene complex in an in vitro culture system involving a brief interaction of macrophages that have phagocytized Listeria monocytogenes and immune T cells. Such cultures contain copious amounts of a thymocyte mitogen, the secretion of which requires homology at the I-A region between the T cell and the macrophage and intimate contact for at least six hours.

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