Development phase

Kinetic examination of cellular changes in regional lymph nodes following local administration of antigen has shown that some of the thymus-dependent lymphocytes, which accumulate in the paracortical zone of the lymph nodes, start to proliferate from the 2nd day on and reach, 3-4 days after first contact with antigen, an immunoblastic, proliferative stage. These immunoblasts (large pyroninophilic cells! revert after mitotic division to small lymphocytes, which appear to be specifically sensitized and are the expression of amplification of some predetermined clones. However, the large proportion of immunoblasts in the lymph node cell population suggests that this proliferation is also to some extent polyclonal, probably under the effect of mitogenic Ivmphokines. The acquisition of specific T lymphocytes, able to produce a DTH reaction, may be evaluated by passive transfer of lymph node cells taken at various times after initial antigen administration. Such passive transfer experiments have shown that specifically sensitized T cells are present in local regional lymph nodes and cause local inflammatory reactions upon renewed contact with antigen. These transfer experiments have also enabled the identification of some T lymphocyte subsets as specifically reactive elements with antigens and responsible for DTH reactions in guinea pigs and in mice. Current evidence suggests that a special subset of CD4 ' X,, 1 lymphocytes is responsible as primary effector cells in DTH reactions.

Recent findings suggest that the nature of antigen presentation by dendritic cells and the lymphokine microenvironment play a decisive role in CD4 1 T cell development leading to suitable effector T lymphocyte subsets for DTH. Interleukin 12 (IL-l2) favors TH1 development and DTH, while IL-10 antagonizes the development of Tnl cells and favors T,,2 lymphocytes. However, there is also evidence that several subsets of lymphocytes may be implicated in DTH and that the TH1/TH2 dichotomy may be an oversimplification.

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