RESUMO
Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8(+) T cells compared with dermal CD14(+) dendritic cells (DCs). Here we show that dermal CD14(+) DCs instead prime a fraction of naïve CD8(+) T cells into cells sharing the properties of type 2 cytokine-secreting CD8(+) T cells (TC2). Differential expression of the CD8-antagonist receptors on dermal CD14(+) DCs, the Ig-like transcript (ILT) inhibitory receptors, explains the difference between the two types of DCs. Inhibition of CD8 function on LCs inhibited cytotoxic T lymphocytes (CTLs) and enhanced TC2 generation. In addition, blocking ILT2 or ILT4 on dermal CD14(+) DCs enhanced the generation of CTLs and inhibited TC2 cytokine production. Lastly, addition of soluble ILT2 and ILT4 receptors inhibited CTL priming by LCs. Thus, ILT receptor expression explains the polarization of CD8(+) T-cell responses by LCs vs. dermal CD14(+) DCs.
Assuntos
Antígenos CD/imunologia , Derme/imunologia , Células de Langerhans/metabolismo , Receptores de Lipopolissacarídeos , Glicoproteínas de Membrana/imunologia , Receptores Imunológicos/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos CD/biossíntese , Antígenos CD/genética , Derme/citologia , Derme/metabolismo , Humanos , Células de Langerhans/citologia , Células de Langerhans/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Receptores Imunológicos/biossíntese , Receptores Imunológicos/genética , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/metabolismoRESUMO
We investigated whether the described immune evasion of Epstein-Barr virus (EBV)-infected malignant Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) is paralleled by a disturbed expression of the signal transduction molecule zeta associated with CD3 and CD16 in tumour-associated T lymphocytes (TAL). Flow cytometric analysis revealed a significantly lower zeta expression in CD3+/4+, CD3+/8+ and CD16+ patient peripheral blood lymphocytes (PBL; n = 10) compared with normal donor PBLs (n = 11). When patient PBLs were compared with the corresponding TAL, the latter showed a significantly higher (CD3+/4+) or equal (CD3+/8+) zeta expression. The EBV status of the tumours did not correlate with zeta expression in the TAL. Immunohistochemical staining revealed zeta-positive lymphocytes among the adjacent bystander cells of the HRS cells in all analysed tumours (n = 8), irrespective of tumour EBV status. In conclusion, these results do not support downregulation of zeta in TAL as a critical mechanism contributing specifically to the immune escape of EBV+ HRS cells.