Auto- and Alloreactivity of T Lymphocytes in Myelodysplastic
Cukrová V., 1Neuwirtová R., 2Bartůňková J., 1Jonášová A., Čermák J., 3Homolková H., 3Malíková I.
Ústav hematologie a krevní transfuze, Praha 1I. interní klinika 1. LF UK a VFN, Praha2Ústav imunologie 2. LF UK, Praha 3Centrální hematologická laboratoř VFN, Praha
Background. Successful therapy with ATG and cyclosporine A in some myelodysplastic syndrome (MDS) patients
led us to study the existence of T cells attacking autologous hemopoietic cells. In our study, we attempted to give the
direct prove of autoreactive T cells in MDS (autoreactivity analysis). Simultaneously, we analysed the capacity of
MDS patients to respond to allogeneic cells from unrelated individuals (alloreactivity analysis).
Methods and Results. Autoreactive lymphocytes directed against own bone marrow mononuclear cells were
analysed using the modification of cell mediated cytotoxic reaction. With one exception we did not confirm the
presence of autoreactive T cells among 10 patients examined. Analysis of alloreactivity was performed by means of
standard cell mediated cytotoxic reaction and mixed lymphocyte reaction. Surprisingly, the cytotoxic response to
allogeneic cells was negative in 11 MDS patients from 16 analysed. When comparing refractory anaemia (RA) and
refractory anaemia with ring sideroblasts (RARS) patients, the proportion of negative results was higher in RA
(78 %) than in RARS (40 %). In mixed lymphocyte reaction, the response of MDS cells to allogeneic cells of
unrelated individual was positive in all tested patients. The preliminary testing of TNF and IFNγ secretion examined
in supernatants of effector cells showed impaired levels of both cytokines in RA and normal levels in RARS in
accordance with the findings achieved in alloreactivity analysis.
Conclusions. Autoreactive T cells were not found in MDS patients using our experimental arrangement. Analysis of
alloreactivity showed the defect in effector -cytotoxic- phase of cell mediated cytotoxic reaction in the majority of
MDS patients. The initial phase of this reaction represented in vitro by mixed lymphocyte reaction gave normal
results. The possible reasons of disturbed alloreactivity and its relevance to immunity in MDS are commented in
myelodysplastic syndrome, cytotoxic T lymphocytes, autoreactivity, alloreactivity, cytokines.