CD8(+) TYPE-1 CD44(HI) CD45 RB(LO) T-LYMPHOCYTES CONTROL INTRACELLULAR BRUCELLA-ABORTUS INFECTION AS DEMONSTRATED IN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-DEFICIENT AND CLASS-II-DEFICIENT MICE

Genetically engineered mice with a targeted disruption in the beta 2-microglobulin (beta 2-m) gene or the H2-I-A beta chain (A beta) which lack functional CD8(+) or CD4(+)T cells, respectively, were used to assess the role of T cell subsets in Brucella abor tus infection. Murine brucellosis was markedly exacerbated in beta 2-m-deficient mice (beta 2-m(+)) compared to A beta mutant (A beta(+)) or C57BL/6 mice, strongly indicating that optimal resistance to B. abortus requires CD8(+) T cells. Splenocytes from Brucella-primed beta 2-m(+), A beta(+) and C57BL/6 mice exhibited a type 1 cytokine profile marked by elevated IFN-gamma mRNA expression and protein production, and basal levels of IL-2 and IL-4 transcripts. B. abortus did not induce secretion of TGF-beta 1, but substantial IL-10 activity was detected in spleen cell supernatants from all mouse strains studied. CD8(+) T cells from A beta(+) and C57BL/6 mice displayed a CD44(hi) CD45RB(lo) phenotype and a type 1 cytokine transcription profile featuring high levels of IFN-gamma mRNA. Additionally, we have shown the ability of C57BL/6 CD8(+) CTL to kill Brucella-infected macrophages. This study illustrates the predominant role of MHC class I-restricted T cells in controlling B. abortus infection.