DIFFERENTIAL ACTIVATION OF TH1 AND TH2 CD4-CELLS AND SMOOTH-MUSCLE PERICYTES( CELLS BY MURINE BRAIN MICROVESSEL ENDOTHELIAL)

CD4+ Th cell infiltration into the brain and the activation by cellula r elements of the central nervous system (CNS) are thought to be impor tant steps in' the initiation of CNS autoimmune diseases. T cell activ ation requires Ag-specific stimulation and additional costimulatory si gnals provided by the APC. Here we describe how murine brain microvess el endothelial (En) cells and smooth muscle/pericytes (SM/P) selective ly induce the Ag-specific activation of different Th1 and Th2 CD4+ T c ell clones. Th1 and Th2 cell clones were used that were specific for t he same peptide Ag in the context of the same class II allotype. SM/P preferentially activated Th1 cell clones, whereas En cells activated T h2 cell clones better, as reflected by cell proliferation and producti on of IL-2 by SM/P-activated Th1 clones and IL-4 by Th2 clones. There was no difference in the level of expression of CD4, CD2, or LFA-1 mol ecules between these Th cell clones, and anti-CD4, CD2, LFA-1 or ICAM- 1 mAb did not differentially affect Ag-induced proliferation among the clones. Moreover, antibody to CD28 did not influence Ag presentation by brain microvessel En or SM/P cells to Ag-specific Th1 and Th2 clone s. These results suggest that: 1) different Th subsets might require d ifferent signals for their activation; 2) different APC might provide different costimulatory signals for Th cell subsets; and 3) brain micr ovessel En and SW/P might play a differential role in induction of aut oreactive T cell responses in the CNS.