Antibodies to the IL-12 receptor beta 2 chain mark human Th1 but not Th2 cells in vitro and in vivo.
Great attention has been placed on the possibility of distinguishing Th1 from Th2 cells on the basis of differential expression of surface receptors. We have recently shown that the differential expression of the IL-12R beta 2 chain in Th1 and Th2 cells, as measured at the mRNA level, accounts for an important regulatory mechanism in the differentiation of the two cell subsets. In this study, we identify IL-12R expression at the protein level. We have generated an anti-IL-12R beta 2-specific mAb and analyzed IL-12R beta 2 expression on polarized Th cell populations generated in vitro and on T cells derived from patients with Th1- or Th2-mediated inflammatory conditions. Although IL-12R beta 2 was absent in freshly isolated PBMC and in cord blood cells, we were able to detect IL-12R beta 2 expression selectively in differentiated Th1 and T cytotoxic 1, but not Th2 or T cytotoxic 2 cells. In the presence of IL-12, cell surface expression of the IL-12R beta 2 subunit was readily detected on T cells after 24 h, reached the maximum at day 5, and declined thereafter. Most importantly, the anti-IL-12R beta 2 mAb recognizes lung T cells from patients with sarcoidosis, a disease characterized by a typical cell-mediated, Th1-type inflammatory response. In contrast, IL-12R beta 2 was absent in lung T cells from patients with allergic asthma, a disease characterized by a Th2-type inflammatory response. The mAb reported in this study should represent a powerful tool to investigate the role of Th1 and Th2 cells in inflammatory conditions and to monitor therapies aimed at altering the balance of Th cell subsets.
Rogge
L
L
Roche Milano Ricerche, Milan, Italy.
Papi
A
A
Presky
D H
DH
Biffi
M
M
Minetti
L J
LJ
Miotto
D
D
Agostini
C
C
Semenzato
G
G
Fabbri
L M
LM
Sinigaglia
F
F
D000328:Adult; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry*; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D012507:Sarcoidosis / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12