Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8(+) T-cell function in Hodgkin lymphoma patients

In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg (HRS) cells constitute only 0.5% of 10% of the diseased tissue. The surrounding cellular infiltrate is enriched with T cells that are hypothesized to modulate antitumor immunity. We show that a marker of regulatory T cells, LAG-3, is strongly expressed on infiltrating lymphocytes present in proximity to HRS cells. Circulating regulatory T cells (CD4(+) CD25(hi) CD45 ROhi, CD4(+) CTLA4(hi), and CD4(+) LAG-3(hi)) were elevated in HL patients with active disease when compared with remission. Longitudinal profiling of EBV-specific CD8(+) T-cell responses in 94 HL patients revealed a selective loss of interferon-gamma expression by CD8(+) T cells specific for latent membrane proteins 1 and 2 (LMP1/2), irrespective of EBV tissue status. Intratumoral LAG-3 expression was associated with EBV tissue positivity, whereas FOXP3 was linked with neither LAG-3 nor EBV tissue status. The level of LAG-3 and FOXP3 expression on the tumor-infiltrating lymphocytes was coincident with impairment of LMP1/2-specific T-cell function. In vitro pre-exposure of peripheral blood mono-nuclear cells to HRS cell line supernatant significantly increased the expansion of regulatory T cells and suppressed LMP-specific T-cell responses. Deletion of CD4(+) LAG-3(+) T cells enhanced LMP-specific reactivity. These findings indicate a pivotal role for regulatory T cells and LAG-3 in the suppression of EBV-specific cell-mediated immunity in HL.

Rethinking the labour movement in the "new South Africa"

The socio-economic system underpinning apartheid in South Africa was based on the exploitation of black workers in the mines, the factories, the fields and the shops. It is widely recognized that the struggles of the South African black working class contributed decisively to the overthrow of the racist regime. In recognition of the power of organised labour, the democratic government elected in 1994 granted South Africa's unions unprecedented legal and constitutional rights. However, despite these gains, the country's labour movement has been facing a fresh set of challenges, from macroeconomic policy to the factory floor, many of them emanating from labour’s political allies in Government. The purpose of this book is to examine how the South African labour movement is responding to these challenges in the new millennium. A variety of experts on South African labour, both within the country and outside deal with crucial issues: How has South Africa's labour movement reacted to the ANC Government's neoliberal economic agenda? How do the unions relate to an increasingly diversifying, “flexible” and vulnerable workforce? What are labour’s prospects of contributing to a left project in democratic South Africa? What are the challenges facing the unions in relation to new forms of militancy and social movements?