Skin-homing CD8+ T lymphocytes show preferential growth in vitro and suppress CD4+ T-cell proliferation in patients with early stages of cutaneous T-cell lymphoma.
A total of 27 T-lymphocyte cell strains were established from skin biopsies of 24 patients with various stages of cutaneous T-cell lymphoma (CTCL) by addition of the T-cell growth factors interleukin (IL)-2 and IL-4. Cellular proliferation and phenotypic changes were measured over 3 months in culture, and T-cell clones were studied using T-cell receptor-? re-arrangement techniques. An average outgrowth of 134 million T-lymphocytes from a 4-mm skin biopsy was observed over 2 months. Initially, most T-cells expressed the CD4+ phenotype. In 17 cell strains from patients with early CTCL a statistically significant predominance of CD8+ T-lymphocytes developed over 8-weeks' culture, indicating that CD8+ T-cells controlled the growth of CD4+ T cells, whereas CD4+ T-cells were predominant in cell strains from advanced CTCL (p <0.05). TCR-? re-arrangement studies revealed, on average, 12 T-cell clones per cell strain, which was reduced over time to 6 T-cell clones per cell strain. Lymphocytes from peripheral blood could kill lymphocytes from an autologous cell strain, suggesting the presence of autoreactive cytotoxic T-cells. Our study suggests how skin-homing CD8+ T-lymphocytes from patients with early stage CTCL can suppress the in vitro growth of skin-homing CD4+ T-lymphocytes, indicating immune surveillance.
Thestrup-Pedersen
Kristian
K
Section of Dermatology, Department of Internal Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. Ktp5@hotmail.com
Parhar
Ranjit
R
Wu
Kaida
K
Bertilsson
Per-Anders
PA
Meyer
Brian
B
Abu-Amero
Sayeda
S
Hainau
Bo
B
Aleisa
Abdullah
A
Alfadley
Abdullah
A
Hamadah
Issam
I
Alajlan
Abdulmajeed
A
Al-Hussein
Khalid
K
Al-Mohanna
Futwan
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D049951:X Chromosome Inactivation / Q000235:genetics
D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4