Characterization of bone marrow T cells in monoclonal gammopathy of undetermined significance, multiple myeloma, and plasma cell leukemia demonstrates increased infiltration by cytotoxic/Th1 T cells demonstrating a squed TCR-Vbeta repertoire.
BACKGROUND
The majority of studies published to date regarding the role of the bone marrow (BM) microenvironment in the pathogenesis of monoclonal gammopathies (MG) have focused on the interaction between stroma cells and plasma cells, whereas information concerning the lymphocytes infiltrating the tumor microenvironment is scanty.


METHODS
The authors measured the distribution, TCR-Vbeta repertoire, immunophenotype, and functional characteristics of different subsets of BM T lymphocytes from 61 nontreated patients with MG (30 patients with MG of undetermined significance [MGUS], 27 patients with multiple myeloma [MM], and 4 patients with plasma cell leukemia [PCL]).


RESULTS
The authors found a significantly increased rate of BM infiltration by T cells in all patient groups, at the expense of CD4+CD8- and CD4-CD8- T lymphocytes and both CD4+CD28- and CD8+CD28- cytotoxic/effector T cell subsets, and associated with TCR-Vbeta expansions in both CD4+ and CD8+ BM T cells in the majority of patients with MGUS, MM, and PCL. Moreover, the percentage of T cells secreting interferon (IFN)-gamma was found to be increased (P < or = 0.05) both in CD4+ and CD8+ T cells in MGUS and MM patients, and a higher plasma concentration of IFN-gamma was found in patients with MM. It is interesting to note that a positive correlation was noted between the proportion of CD28- and both the percentage of IFN-gamma-secreting cells and the proportion of expanded TCR-Vbeta lymphocytes within the total BM CD4+ T cells.


CONCLUSIONS
The results of the current study demonstrated an increased infiltration of BM by T cells associated with frequent TCR-Vbeta expansions and a more prominent cytotoxic/Th1 phenotype in all the patient groups studied.
Cytometry Service, Department of Medicine, University of Salamanca, Salamanca, Spain.
Martin
M
Pérez-Andres
Julia
J
Almeida
Marta
M
Martin-Ayuso
Maria Jesus
MJ
Moro
Guillermo
G
Martin-Nuñez
Josefina
J
Galende
Jose
J
Hernandez
Gema
G
Mateo
Jesus F
JF
San Miguel
Alberto
A
Orfao
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007952:Leukemia, Plasma Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010265:Paraproteinemias / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma