Susceptibility of β₂-microglobulin-deficient mice to Trypanosoma cruzi infection

Abstract

THE β₂microglobulin (β₂m) protein associates with the products of the class I major histocompatibility (MHC) loci; this combination functions in the thymic development of and antigen presentation to CD8⁺ T cells. Mice in which the β₂m gene has been disrupted by homologous recombination fail to express class I MHC gene products, and therefore lack CD8⁺ T cells and measurable cytotoxic T-cell responses^1,2. However, β₂m− mice appear to have normal development of both CD4⁺ α/βT-cell receptor (TCR⁺) and γ/δ TCR⁺ T cells and are not overtly more susceptible than β₂m⁺ mice to potential environmental agents of infection^1,2 or to experimental viral infection³. Here we show that β₂m⁻ mice suffer high parasitaemias and early death when infected with the obligate cytoplasmic protozoan parasite Trypanosoma cruzi. Despite this increased susceptibility, the β₂m⁻ mice are more responsive than their β₂m⁺ littermates in terms of lymphokine production, making higher levels of both interleukin-2 and interferon-γ in response to mitogen stimulation. In addition, theβ₂m− mice show essentially no inflammatory response in parasite-infected tissues. These results confirm previous experiments on mice depleted of CD8⁺cells using antibody treatment4 in demonstrating the importance of CD8⁺ T cells in immune protection in T. cruzi infection. They also implicate CD8⁺ T cells and/or class I MHC molecules in regulation of lymphokine production and recruitment of inflammatory cells.