Plasmodium falciparum and P. vivax Gametocyte-Specific Exoantigens Stimulate Proliferation of TCR γδ + Lymphocytes

Abstract

Immune modulation of Plasmodium vivax and P. falciparum gametocytes occurs over the course of erythrocytic infection. The response is linked to proliferative and inflammatory responses, which may be stimulated by stage-specific gametocyte proteins. Stage-specific exoantigens were purified from supernatants of P. falciparum and P. vivax gametocyte cultures, and either primary or secondary postinfection lymphocytes were stimulated for proliferation. Five of 25 exoantigens purified from P. falciparum gametocyte cultures and 6 of 28 exoantigens isolated from P. vivax were gametocyte stage specific. Metabolic labeling of soluble P. falciparum gametocyte proteins confirmed synthesis and secretion of 5 stage-specific exoantigens, with molecular masses of 118, 62, 52, 37, and 33 kDa. Purified gametocyte exoantigens within the range of 50 to 100 kDa stage-specifically stimulated proliferation of lymphocytes from postprimary P. falciparum infections, and from postprimary and secondary P. vivax infection patients with homologous purified exoantigens. T-cell receptor (TCR)gammadelta+, and CD3+ CD8+ and CD3+ CD4- CD8- T cells were specifically upregulated from P. falciparum primary- and P. vivax secondary-infection lymphocytes, respectively, using gametocyte stage-specific exoantigens. CD25+ was the major activation marker expressed by CD3+ and gammadelta T cells when stimulated with gametocyte exoantigens. None of the T cell markers was significantly upregulated using gametocyte stage-specific exoantigens with primary-infection P. vivax lymphocytes.

Hepatosplenic T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients

“…[63][64][65][66][67][68] The depletion of ␥␦ ⌻ cells has proved to dramatically reduce the severity of rheumatoid arthritis in a mouse model. 58 Furthermore, Plasmodium falciparum exoantigens have been shown to stimulate the proliferation of ␥␦ T-lymphocytes in patients after primary infection, 69 and accumulations of these cells have been observed in the spleens and peripheral blood of patients with P falciparum malaria. 2,70 Finally, ␥␦ ⌻ cells, which are known to participate in the immune response to several viruses, 71 can respond in vitro to EBV-infected human Burkitt cell lines.…”

Proteome Analysis of Plasmodium falciparum Extracellular Secretory Antigens at Asexual Blood Stages Reveals a Cohort of Proteins with Possible Roles in Immune Modulation and Signaling

“…Parasite factors such as surface proteins and secretory molecules can directly suppress the function of certain subsets of immune cells as well as stimulate other cell populations that have suppressive activity like the regulatory T cells (43). A previous study has reported that P. falciparum and Plasmodium vivax gametocyte-specific exoantigens stimulate proliferation of T cell receptor ␥␦ ϩ lymphocytes (44). The LCCL family of Apicomplexaspecific proteins (PfCCP1 in our data) has also been reported to play a role in host immune evasion (23).…”

Mycobacterium-Specific γ9δ2T Cells Mediate Both Pathogen-Inhibitory and CD40 Ligand-Dependent Antigen Presentation Effects Important for Tuberculosis Immunity

“…␥ 9 ␦ 2 T cells proliferate and develop relevant effector functions in response to M. tuberculosis (15), HIV (16), Plasmodium spp. (17), and many other human pathogens (18)(19)(20)(21)(22). Furthermore, depletion of circulating ␥ 9 ␦ 2 T cells during infections with different pathogens has been associated with increased susceptibility to more severe disease (23)(24)(25).…”