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. 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 2m+ mice to potential environmental agents of infection or to experimental viral infection. 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 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.
Tarleton
R L
RL
Department of Zoology, University of Georgia, Athens 30602.
Koller
B H
BH
Latour
A
A
Postan
M
M
D000208:Acute Disease; D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D014355:Chagas Disease / Q000276:immunology*; D002908:Chronic Disease; D006321:Heart / Q000469:parasitology; D007153:Immunologic Deficiency Syndromes / Q000469:parasitology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D009132:Muscles / Q000469:parasitology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency*
D016827:CD8 Antigens; D007376:Interleukin-2; D001613:beta 2-Microglobulin; D007371:Interferon-gamma