Cutaneous lymphocyte antigen expression on activated lymphocytes and its association with IL-12R (beta1 and beta2), IL-2Ralpha, and CXCR3.
The majority of T lymphocytes that infiltrate psoriatic lesions express cutaneous lymphocyte antigen (CLA), a skin homing receptor involved in the influx of memory T cells to cutaneous sites. We investigated CLA expression on normal human peripheral blood mononuclear cells (PBMCs) and evaluated its association with IL-12 receptors, chemokine receptor, CXCR3, and IL-2Ralpha. PBMCs were stimulated in vitro with or without polyclonal activators (mitogen, or superantigens, or anti-CD3+anti-CD28) in the presence or absence of exogenous rhIL-12. The percentage of CLA+ T lymphocytes increased significantly after superantigen stimulation compared to anti-CD3+anti-CD28 or mitogen activation. The majority of activation induced CLA+ T lymphocytes co-expressed IL-12Rbeta1, IL-12Rbeta2, CXCR3, and CD25 in the presence of rhIL-12. Our results indicate that CLA expression on activated T lymphocytes is IL-12 and activation dependent and correlates with the expression of IL-12 receptors, IL-2Ralpha, and CXCR3. Monitoring the levels of Th1 differentiation markers such as CXCR3 and IL-12Rbeta2 along with activation marker, CD25 on skin homing CLA+ T lymphocytes may provide insight into the mechanism of action of immunotherapies directed against Th1 type skin inflammatory diseases.
Reddy
Manjula
M
Department of Clinical Pharmacology and Experimental Medicine, Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087-4517, USA. Mreddy@CNTUS.JNJ.com
Davis
Cuc
C
Wong
Jackson
J
Prabhakar
Uma
U
D000906:Antibodies / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins / Q000494:pharmacology; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D018106:CD28 Antigens; D017252:CD3 Complex; C063419:CTAGE1 protein, human; C515187:CXCR3 protein, human; C508438:IL12RB1 protein, human; C508439:IL12RB2 protein, human; D008562:Membrane Glycoproteins; D008934:Mitogens; D010835:Phytohemagglutinins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins; D018089:Superantigens; C028784:phytohemagglutinin-P; D018664:Interleukin-12