Human astrocytes are only partially competent antigen presenting cells

Abstract
Highly purified astrocyte cultures from human embryonic brain were examined for their capacity to present antigen to human leukocyte antigen (HLA) class II compatible, cytotytic CD4+ T lymphocytes. Most astrocytes constitutively expressed HLA class I products and LFA-3 (CD58). Constitutive expression of HLA class II, LFA-Iα (CDIIa) and ICAM-I (CD54) was lower and varied among different cultures, while LFA-2 (CD2) was absent. IFN-γ alone or in combination with TNF-α strongly enhanced expression of HLA class I, HLA-DR, -DP, -DQ, LFA-lα and ICAM-I, but did not affect expression of LFA-2 (CD2) and LFA-3 (CD58). TNF-α alone induced only HLA class I and ICAM-I, but not HLA class II or LFA-lα. Cytokine treated, but not untreated astrocytes were able to present protein (auto-)antigens to specific T lymphocyte lines. Astrocytes expressing appropriate major histocompatibility complex class II products were lysed by CD4+ T cells specific for myelin basic protein or tetanus toxoid. The lytic response was antigen dose dependent and HLA-DR restricted. It could be blocked by antibodies against HLA-DR determinants and against the adhesion molecules LFA-lα and ICAM-I. In remarkable contrast to their susceptibility to T cell lysis, antigen presenting astrocytes were not only completely unable to induce T cell proliferation but even inhibited proliferation. The results indicate that, although human astrocytes have the potential to present protein antigens to CD4+ T cells, they do not induce the costimulatory factors required to trigger the complete T cell activation programme.

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