Changes in circulating lymphocyte subpopulations following administration of the leucocyte function-associated antigen-3 (LFA-3)/IgG1 fusion protein alefacept.
Alefacept, a recombinant leucocyte function-associated antigen-3 (LFA-3)/IgG1 fusion protein approved for the treatment of psoriasis, is reported to reduce selectively the numbers of circulating CD4(+) CD45RO(+) and CD8(+) CD45RO(+) T cells, while sparing the naive cells. The purpose of the present study was to elucidate further the effect of alefacept on various circulating lymphocyte subsets. Sixteen patients, 12 with chronic plaque psoriasis and four with pustular psoriasis, received alefacept 7.5 mg once weekly for 12 weeks. Blood samples collected at study entry and after 12 weeks of treatment were analysed by four-colour flow cytometry. There were statistically significant reductions in the total number of conventional memory (CD45RA(-) CD27(+)) and effector (CD45RA(-) CD27(-) or CD45RA(+) CD27(-)) T cells, including CD4(+) and CD8(+) T cells expressing CD161 and CD8(+) T cells expressing cutaneous lymphocyte-associated antigen (CLA). Natural killer (NK) T cells were also reduced significantly, while no statistically significant changes were seen in NK cells and CD4(+) CD25(high) cells. The affected subpopulations were all characterized by a high expression of CD2. However, CD4(+) CD25(low), and CD4(+) CLA(+) cells, which also expressed relative high levels of CD2, were not reduced significantly. Our results suggest a heterogeneous effect of alefacept on the circulating memory T cell population, indicating that high expression of CD2 may not, by itself, be sufficient to explain the reduction in cell count for a specific subpopulation.
Larsen
R
R
Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark. runel@dadlnet.dk
Ryder
L P
LP
Svejgaard
A
A
Gniadecki
R
R
D000328:Adult; D000368:Aged; D000077944:Alefacept; D018801:CD2 Antigens / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects; D018655:Lymphocyte Count; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D016896:Treatment Outcome
D018801:CD2 Antigens; D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077944:Alefacept; D008727:Methotrexate