SUSCEPTIBILITY OF BETA-2-MICROGLOBULIN-DEFICIENT MICE TO TRYPANOSOMA-CRUZI INFECTION

THE beta-2-microglobulin (beta-2m) 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 beta-2m 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, beta-2m- mice appear to have normal development of both CD4+ alpha/beta-T-cell receptor (TCR+) and gamma/delta-TCR+ T cells and are not overtly more susceptible than beta-2-m+ mice to potential environmental agents of infection 1,2 or to experimental viral infection 3. Here we show that beta-2m- mice suffer high parasitaemias and early death when infected with the obligate cytoplasmic protozoan parasite Trypanosoma cruzi. Despite this increased susceptibility, the beta-2m- mice are more responsive than their beta-2m+ littermates in terms of lymphokine production, making higher levels of both interleukin-2 and interferon-gamma in response to mitogen stimulation. In addition, the beta-2m- mice show essentially no inflammatory response in parasite-infected tissues. These results confirm previous experiments on mice depleted of CD8+ cells using antibody treatment 4 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.