INDEPENDENT REGULATION OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION AND CYTOKINE SYNTHESIS PHENOTYPE DURING HUMAN CD4(-CELL DIFFERENTIATION() MEMORY T)

Although considerable attention has been paid to the development of cy tokine synthesis heterogeneity during memory T cell differentiation, l ittle information is available on how this function is coregulated wit h homing receptor expression. The development of skin-homing, CD4(+) m emory T cells in the human provides an excellent model for such invest igation, since 1) the skin supports both Th1- and Th2-predominant resp onses in different settings, and 2) the skin-homing capability of huma n memory T cells correlates with and appears to depend on expression o f the skin-selective homing receptor cutaneous lymphocyte-associated A g (CLA). In this study, we used multiparameter FACS analysis to examin e expression of CLA vs IFN-gamma, IL-4, and IL-2 synthesis capabilitie s among fresh peripheral blood CD4(+) memory T cells, and Th1 vs Th2 m emory T cells generated in vitro from purified CD4(+) naive precursors by cyclic activation in polarizing culture conditions. Among normal p eripheral blood T cells, CU expression was essentially identical among the IFN-gamma-vs IL-4-producing CD4(+) memory subsets, clearly indica ting the existence of in vivo mechanisms capable of producing both Th1 vs Th2 skin-homing T cells. In vitro differentiation of naive CD4(+) T cells confirmed the independent regulation of CLA and all three cyto kines examined, regulation that allowed differential production of IFN -gamma-, IL-4-, and IL-2-producing, CLA(+) memory subsets. These studi es also 1) demonstrated differences in regulatory factor activity depe nding on the differentiation status of the responding cell, and 2) rev ealed CLA expression to be much more rapidly reversible on established memory cells than cytokine synthesis capabilities.