HUMAN VDELTA1 T CELLS REPRESENT A DOMINANT GAMMA-DELTA T CELL SUBSET IN PATIENTS WITH MULTIPLE MYELOMA

Background:

Human γδ T cells are potent effector lymphocytes of innate immunity involved in anti-tumor immune surveillance. However, the role of Vδ1 γδ subset in patients progressing from monoclonal gammopathy of undetermined significance (MGUS) to Multiple Myeloma (MM) in this process is unknown. We have recently shown that Vδ1 lymphocytes isolated from myeloma patients exert specific cytotoxicity against primary CD38+CD138+ bone marrow derived plasma cells (Knight et al., Cytotherapy 2012).

Aims:

We aimed to determine the frequencies and phenotypes of Vδ1 and Vδ2 γδ T cell populations in MGUS patients, newly diagnosed myeloma patients, and treated myeloma patients. We hypothesized that the innate immune responses are gradually deregulated in patients progressing from MGUS to MM and this leads to changes in T cell distribution.

Methods:

Fresh whole bone marrow samples were used from MGUS (n=25), newly diagnosed myeloma (n=41) and treated myeloma patients (n=7). We used multicolor flow cytometric analysis to determine the naive/memory/effector phenotypes in patient cohorts and to compare the data with healthy donors.

Results:

In MGUS patients, the median levels of Vδ1 and Vδ2 cells were 2.19 (range 0.55-8.05) and 0.63 (0.04-10.2) of CD3+ T cells respectively. Interestingly, largely elevated Vδ1 cells compared to healthy donors were predominantly of naive phenotype CD27+CD45RA+ in these patients. In contrast, Vδ1 cells in newly diagnosed MM patients and patients after treatment showed effector memory CD27+CD45RA- and terminally differentiated phenotype of CD27- CD45RA+ expression. More importantly, we detected continuously expanded frequencies of Vδ1 cells in both cohorts of MM patients, (range 0.19-17.50 and 1.35-7.50 respectively). The Vδ2 cell subset was also expanded in MM patient cohorts, however the medians were overall reduced compared to the Vδ1 population. The Vδ2 cells were mostly of memory phenotype with CD27+CD45RAexpression in all patient cohorts.

Summary / Conclusion:

Our results show significantly elevated frequencies of Vδ1 γδT cell subset in patients progressing from MGUS to MM indicating a possible compensation for defects in specific T-cell immunity. Given that the Vδ1 subset shows a very restricted TCR repertoire compared to the Vδ2 subset, the overall capacity of γδ T cells to recognise and respond to antigens in the bone marrow microenvironment might be significantly enhanced by the interactions with other cell types. The role of large expansions of Vδ1 cells and factors leading to myeloma progression remain to be elucidated. Nevertheless, this is the first report analyzing the Vδ1 cells in patients with monoclonal gammopathy.

The project has been funded by the Royal Free Charity, and IGA NT 11145-4, IGA 12130-4, MSMT 0021622434, P304/10/1395 grants.

Abstrakta v časopise Haematologica 2013, Suppl1

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