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 γδ T‐cell lymphoma following seven malaria infections

“…γδΤ‐cells participate in the immune response against Plasmodium sp. although their role is unclear 24,25 . Expansion of the Vδ2 (Vγ9/Vδ2) subset occurs in response to non‐peptide, phosphorylated antigens of P. falciparum and P. vivax 25 .…”

“…although their role is unclear 24,25 . Expansion of the Vδ2 (Vγ9/Vδ2) subset occurs in response to non‐peptide, phosphorylated antigens of P. falciparum and P. vivax 25 . Conversely, expansion of Vδ1 T cells is not characteristic of infectious diseases but it has been described in HIV infection, infectious mononucleosis and some autoimmune disorders 26,27 .…”

A Unique Subset of γδ T Cells Expands and Produces IL-10 in Patients with Naturally Acquired Immunity against Falciparum Malaria

“…A polyclonal population of γδ T cells may be necessary to counter the antigenic diversity present in malarial infections (Covell et al, 1953; Healer et al, 2004). Malarial antigens for human γδ T cells have been identified as soluble Pf-schizont-associated antigens, including phosphate antigens (Behr et al, 1996; Pichyangkul et al, 1997) and gametocyte-specific antigens (Ramsey et al, 2002). However, there is little information on non-Vγ9 T cell-specific antigens (Vantourout and Hayday, 2013).…”

Immune Responses to the Sexual Stages of Plasmodium falciparum Parasites

“…Gametocyte-specific exoantigens (from gametocyte culture supernatants) have been shown to be able to stimulate the proliferation and activation of lymphocytes from P. falciparum exposed individual (72). In this study, T cell receptors gamma/delta (TCR γδ+), and CD3 + CD8 + and CD3 + CD4 − CD8 − T cells were found to be up-regulated upon sensitization with these exoantigens.…”