Systemic and local expression of perforin in lymphocyte subsets in acute and chronic rheumatoid arthritis.
OBJECTIVE
To investigate the role of the cytolytic action mediated by perforin in the course of rheumatoid arthritis (RA), we studied the immunophenotypic characteristics of lymphocytes containing perforin in peripheral blood (systemic level), in synovial fluid (SF), and in the synovial membrane (local level) in patients during the acute or chronic phase of RA. Cells from patients with osteoarthritis were used as controls.


METHODS
Flow cytometry was used for simultaneous detection of intracellular (perforin) and cell surface antigens. Mean fluorescence intensity (MFI) was a measure of the mean perforin content per cell. Immunocytochemical staining was used to visualize perforin in the cytoplasmic compartment of cells.


RESULTS
In acute RA highly significant changes in perforin expression were found in all compartments (peripheral blood, SF, and synovial membrane): (1) increase of percentage of total perforin positive cells; (2) increase of both subsets of cytolytic cells, T (CD8+P+) and NK (CD56+P+) cells; (3) increase in the frequency of perforin positive cells in CD8+ and CD56+ cell populations; and (4) the highest content of perforin/cell (MFI values) in all compartments, except in the synovial membrane.


CONCLUSIONS
Perforin positive cells may participate in the acute phase of RA by maintaining and perpetuating inflammation and contributing to tissue destruction.
Gulan
Gordan
G
Department of Orthopaedic Surgery, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Ravlic-Gulan
Jagoda
J
Strbo
Natasa
N
Sotosek
Vlatka
V
Nemec
Boris
B
Matovinovic
Damir
D
Rubinic
Dusan
D
Podack
Eckhard R
ER
Rukavina
Daniel
D
D000208:Acute Disease; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D002908:Chronic Disease; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000737:chemistry; D016131:Lymphocyte Subsets / Q000737:chemistry*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D017452:Receptors, IgG / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry
D019002:CD56 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D054353:Perforin