HUMAN ASTROCYTES ARE ONLY PARTIALLY COMPETENT ANTIGEN-PRESENTING CELLS - POSSIBLE IMPLICATIONS FOR LESION DEVELOPMENT IN MULTIPLE-SCLEROSIS

Highly purified astrocyte cultures from human embryonic brain were exa mined for their capacity to present antigen to human leukocyte antigen (HLA) class II compatible, cytolytic CD4(+) T lymphocytes. Most astro cytes constitutively expressed HLA class I products and LFA-3 (CD58). Constitutive expression of HLA class II, LFA-1 alpha (CD11 alpha) and ICAM-1 (CD54) was lower and varied among different cultures, while LFA -2 (CD2) was absent. IFN-gamma alone or in combination with TNF-alpha strongly enhanced expression of HLA class I, HLA-DR, -DP, -DQ, LFA-1 a lpha and ICAM-1, but did not affect expression of LFA-2 (CD2) and LFA- 3 (CD58). TNF-alpha alone induced only HLA class I and ICAM-1, but not HLA class II or LFA-1 alpha. Cytokine treated, but not untreated astr ocytes were able to present protein (auto-)antigens to specific T lymp hocyte lines. Astrocytes expressing appropriate major histocompatibili ty complex class II products were lysed by CD4(+) T cells specific for myelin basic protein or tetanus toroid. The lyric response was antige n dose dependent and HLA-DR restricted It could be blocked by antibodi es against HLA-DR determinants and against the adhesion molecules LFA- 1 alpha and ICAM-1. In remarkable contrast to their susceptibility to T cell lysis, antigen presenting astrocytes were nor only completely u nable to induce T cell proliferation but even inhibited proliferation. The results indicate that, although human astrocytes have the potenti al to present protein antigens to CD4(+) T cells, they do not induce t he co-stimulatory factors required to trigger the complete T cell acti vation programme.