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Differential inhibition of the MLR by iron: association with HLA phenotype
Abstract:
The effect of iron on the MLR was examined by pretreating peripheral blood mononuclear cells from 77 unrelated Caucasians with five concentrations of Ferric-citrate (10.0 mM, 1.0 mM, 0.1 mM, 0.01 mM and 0.005 mM). After incubation with the metal, the cells were washed and cultured in a one-way MLR with a pool of stimulator cells. Cell viability remained unchanged (greater than 90 percent) during the 6-day culture period. Citrate per se had no effect on either the responder or the stimulator population. Iron treatment influenced the MLR in the following ways: (1) a variable degree of inhibition was observed which related to the dose of Ferric-citrate used and to HLA phenotype, (2) the responder but not the stimulator cells were affected, (3) no statistically significant differences were seen between female and male donor cells and (4) the mean percent response of cells from HLA-A2 donors were significantly (0.005 less than P less than 0.01) less susceptible to iron exposure than those from non-HLA-A2 individuals. The present results indicate that iron can interact with lymphoid cells and influence some immunological functions in vitro. The possibility is discussed that similar interactions take place in vivo which could contribute to the prognosis of certain diseases associated with particular HLA phenotypes.
Insights
Iron exposure inhibits mixed lymphocyte reactions (MLR) in a dose-dependent manner, affecting responder cells and varying with HLA phenotype. This suggests iron influences immune function, potentially impacting disease prognosis.
Area of Science:
- Immunology
- Hematology
- Medical Science
Background:
- The mixed lymphocyte reaction (MLR) is a key measure of T-cell mediated immune response.
- Investigating the impact of essential trace elements like iron on immune cell function is crucial for understanding health and disease.
Purpose of the Study:
- To determine the in vitro effect of ferric-citrate on the mixed lymphocyte reaction (MLR).
- To explore the relationship between iron's immunomodulatory effects and human leukocyte antigen (HLA) phenotype.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from 77 Caucasians were pretreated with varying concentrations of ferric-citrate.
- Cells were then cultured in a one-way MLR assay.
- Cell viability, MLR response, and influence of HLA type were assessed.
Main Results:
- Ferric-citrate inhibited the MLR in a dose-dependent manner, primarily affecting responder cells.
- The degree of inhibition varied with HLA phenotype, with HLA-A2 positive donors showing less susceptibility.
- Citrate alone and cell viability were unaffected; no sex-based differences were observed.
Conclusions:
- Iron interacts with lymphoid cells, modulating immune responses in vitro.
- These findings suggest a potential in vivo role for iron in immune function and disease prognosis, particularly in relation to specific HLA types.