CD8+ T cells in Trypanosoma cruzi infection

Abstract

CD8(+) T cells have emerged as crucial players in the control of a number of protozoan pathogens, including Trypanosoma cruzi, the agent of human Chagas disease. The recent identification of the dominant targets of T. cruzi-specific T cells has allowed investigators to follow the generation of and document the functionality of T cell responses in both mice and humans. Although slow to develop in the early stages of the infection, T. cruzi-specific CD8(+) T cells reach prodigious levels and remain highly functional throughout chronic infections in mice. Following drug-induced cure during either the acute or chronic stage, these immunodominant T cells persist as stable, antigen-independent memory populations. T. cruzi-specific CD8(+) T cells in humans are less-well-studied but appear to lose functionality and decline in numbers in these decades-long infections. Changes in the frequency of parasite-specific T cell upon therapeutic treatment in humans may provide a new metric for determining treatment efficacy.

Figure 1

Alignment of regions of selected trans-sialidase genes from related Trypanosomatids showing homologies to the H2K^b binding motif XX(Y,P)X(F,Y)XX(V,L,M,I): A set of trans-sialidase protein sequences from T. brucei (prefix “Tb”), T. brucei gamiense (“Tbgamb”), T. congolense (“congo”), T. vivax (“Tviv”), T. rangelli (“Tr”) were aligned with a TSKb-20-containing region from a single T. cruzi (“Tc”) trans-sialidase family gene (Tc10275.35). The TSKb20 peptide (ANYKFTLV) is underlined. The gray-scale shading indicates the degree of homology at that particular residue (black=perfect identity, gray=conserved, white=non-conserved).