Efalizumab (anti-CD11a)-induced increase in peripheral blood leukocytes in psoriasis patients is preferentially mediated by altered trafficking of memory CD8+ T cells into lesional skin.
Therapeutic administration of efalizumab, a humanized antibody to CD11a, induces a marked but reversible increase of peripheral lymphocytes in psoriasis patients. In this study, 13 patients were treated with 12 weekly subcutaneous doses (2 mg/kg/week) of efalizumab, and all 13 patients had increases in leukocyte counts. This increased white blood cell count was mainly due to a 3- to 4-fold increase in the number of circulating CD3(+) lymphocytes during active treatment. Both naive and memory populations of CD4(+) and CD8(+) lymphocytes in the peripheral blood increased, with the largest increase observed in memory CD8(+) T cells. This CD8(+) memory T cell subset is a prominent T cell population found in psoriatic skin. An increase in Type 1 (IFN-gamma producing) T cells was also observed during treatment. Both components of LFA-1, CD11a and CD18, were downregulated during treatment, and surprisingly the integrins CD11b and beta 7 were similarly reduced. We conclude that efalizumab most likely blocks cutaneous entry of memory CD8(+) T cells, a highly disease-relevant cell population. The relatively smaller increase in naive peripheral blood T cells could be attributed to reduced trafficking of naive T cells.
Vugmeyster
Yulia
Y
Genentech, Inc., South San Francisco, CA, USA.
Kikuchi
Toyoko
T
Lowes
Michelle A
MA
Chamian
Francesca
F
Kagen
Mark
M
Gilleaudeau
Patricia
P
Lee
Edmund
E
Howell
Kathy
K
Bodary
Sarah
S
Dummer
Wolfgang
W
Krueger
James G
JG
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D040881:CD11a Antigen; D015815:Cell Adhesion Molecules; C472181:efalizumab