CD8+ T cells in cutaneous T-cell lymphoma: expression of cytotoxic proteins, Fas Ligand, and killing inhibitory receptors and their relationship with clinical behavior.
OBJECTIVE
We investigated the number, phenotype, and prognostic significance of CD8+ T cells in patients with mycosis fungoides (MF) and CD30- primary cutaneous large T-cell lymphoma (PCLTCL).


METHODS
Immunohistochemical stainings for CD8, granzyme B (GrB), T cell-restricted intracellular antigen (TIA-1), Fas ligand (FasL), and killer-cell inhibitory receptors (KIRs; CD95, CD158a, and CD158b) were performed on 83 first-diagnostic biopsy samples obtained from patients with plaque-stage MF (n = 42), tumor-stage MF (n = 20), and CD30- PCLTCL (n = 21).


RESULTS
Serial sections and double-staining experiments showed that the large majority of CD8+ T cells in MF and CD30- PCLTCL expressed TIA-1 and FasL, whereas only a minority expressed GrB, which suggested that these CD8+ T cells were partly activated cytotoxic T lymphocytes (CTLs). These CD8+ CTLs never or rarely expressed KIRs. This phenotype was a constant feature of CD8+ CTLs and did not alter with disease progression. In contrast, the median percentage of CD8+ CTLs in plaque-stage MF (22%), tumor-stage MF (7%), and CD30- PCLTCL (3%) differed significantly (P < .0001) and was associated with a significant decrease in 5-year survival. Also within the group of tumor-stage MF, a significant relation between CD8+ CTLs and survival was found. Multivariate analysis in the total group of MF demonstrated that both skin stage and percentage of CD8+ CTLs were independent parameters of survival.


CONCLUSIONS
Our results demonstrated that partly activated CD8+ CTLs were present in CTCL and that high proportions of these cells correlated with a better prognosis. This suggested that these CD8+ CTLs could play an important role in the antitumor response in these conditions.
Vermeer
M H
MH
Department of Dermatology, Free University Hospital, Amsterdam, the Netherlands. m.h.vermeer@lumc.nl
van Doorn
R
R
Dukers
D
D
Bekkenk
M W
MW
Meijer
C J
CJ
Willemze
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D018572:Disease-Free Survival; D053222:Fas Ligand Protein; D005260:Female; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009426:Netherlands; D039102:Poly(A)-Binding Proteins; D011379:Prognosis; D011506:Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D012697:Serine Endopeptidases / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases