Human naive T cells are preferentially stimulated by crosslinking of CD3 and CD45RA with monoclonal antibodies.
To analyze the role of CD45 molecules in CD3-mediated activation of T cells, we analyzed the effect of crosslinking different CD45 isoforms with mAbs on the proliferation of various T cell subsets in vitro. Crosslinking of CD3 and CD45RA molecules with the mAb 2H4 or WR16 resulted in the preferential stimulation of enriched naive (CD45RA+) T cells, whereas crosslinking of CD3 alone led to stimulation of enriched memory (CD45RO+) T cells. In contrast, proliferation of memory T cells was not enhanced by additional crosslinking with the memory T cell marker CD45RO. To induce the costimulatory effect on naive T cells, an intense crosslinking of the TcR/CD3 complex and CD45RA molecules by immobilized secondary antibody is necessary because enhanced proliferation did not occur when the antibodies were directly immobilized. The same differences in reactivity of CD45RA-enriched naive and CD45RO-enriched memory T cell subset could be shown by using a mAb to common CD45, indicating that the effects are not mediated by a particular antibody or by binding to different epitopes. The CD45RA-induced differences in proliferation of naive and memory T cells could not be abolished by the addition of exogenous IL2. In contrast, naive T cells were more responsive to exogenous IL2 than memory T cells independently of CD45RA crosslinking, indicating that IL2 is not responsible for the observed differences in T cell proliferation.
Department of Immunopharmacology, E. Merck, Darmstadt, Germany.
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T
Welge
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M
Wolf
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Jäggle
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Luckenbach
D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D017493:Leukocyte Common Antigens