Complex mechanisms regulate T cell anergy during the acute phase of Trypanosoma cruzi infection.

ANA, YAMILE; ROJAS MARQUEZ, JORGE D.; CERBAN, FABIO M.; STEMPIN, CINTHIA C.

Mar del Plata, Buenos Aires

Congreso; LXIV Reunión anual de la Sociedad Argentina de Inmunología.; 2016

Sociedad Argentina de Inmunología

We have previously shown that decreased T cell proliferationduring acute phase of Trypanosoma cruzi infection is relatedto increase of inhibitory receptor and gene related to anergy inlymphocytes (GRAIL) expression, reduced IL2 production and expressionof its regulator Otubain 1 (Otub-1). The aim of this studywas to evaluate if GRAIL expression during infection is regulatedby IL-2. BALB/c mice were infected i.p. with 500 trypomastigotesof Tulahuen strain and CD4+T cells were purified from spleen ofuninfected or infected mice at 21 days post infection (d.p.i). First,we measured whether impaired proliferative response could bereversed by adding IL-2. CD4+T cells from control and 21 d.p.ianimals were stimulated with anti-CD3/CD28 in the presence orabsence of IL-2 for 3 days and then cell proliferation was assessedby CFSE. We found that CD4+T cells from control as well as 21d.p.i animals had an increase in proliferation when treated withIL-2 together with the TCR stimulatory ligands. In addition, wealso evaluated GRAIL and Otub-1 expression as well as mTORactivation in CD4+T cells with or without IL-2. In agreement withthe increase in CD4+T cell proliferation, we found a slight rise inthe phosphorylation of 4EBP1 (mTOR) and Otub-1 expression anda reduction in GRAIL expression. Besides we observed by FACSan increase in GRAIL expression in naïve and memory CD4+T cellpopulation (p<0.05 vs control). Furthermore, we tested if GRAILexpression could be induced directly and by different parasitestrains. To perform this, CD4+T cells purified from BALB/c micewere incubated with Tulahuen or Y strain and 24h later GRAILexpression was assess by intracellular FACS staining. We haveobserved that both stains are able to induce GRAIL expression invitro. These results may indicate that although GRAIL expressioncould be induced directly by different parasite strains its regulationmay implicate a complex mechanism involving Otub-1, mTORactivation and IL-2.