CD27, a member of the nerve growth factor receptor family, is preferentially expressed on CD45RA+ CD4 T cell clones and involved in distinct immunoregulatory functions.
CD27 is a disulfide-linked 120-kDa homodimer expressed on the majority of peripheral T cells at variable density that belongs to the recently defined nerve growth factor receptor family. mAb reactive with CD27 can either enhance or inhibit T cell activation, suggesting a crucial role in the process of T cell activation. We now show that CD27 is preferentially expressed on the CD45RA+CD45RO-CD29low subset of CD4 cells. CD27 expression on this subset is maintained for a prolonged period in culture after PHA activation. In contrast, CD45RA-CD45RO(+)-CD29high subset of CD4 cells express very low level of CD27, and its expression is lost within 2 wk after PHA activation. To further analyze the differential expression of CD27 on these reciprocal subsets of CD4 cells, we developed T cell clones by stimulating isolated CD4+CD45RA+ and CD4+CD45RO+ populations with PHA. T cell clones derived from cells originally CD45RA+ retained both CD45RA and CD27 expression, whereas T cell clones derived from cells originally CD45RO+ were CD45RA- and CD27-. In functional assays, IL-4 production could only be induced in CD45RA-CD27- CD4 clones by stimulation with PMA and ionomycin. Four of six CD45RA+ CD4 clones had suppressor activity in PWM-driven IgG synthesis, whereas five of six CD45RA- CD4 clones had helper activity. Of interest, the suppressor activity of CD45RA+CD27+ clones was partially blocked by pretreatment with anti-CD27 mAb (1A4). Anti-1A4 pretreatment of these T cell clones resulted in elevation of intracellular cAMP levels. Thus, CD27 appears to play a role in the function of CD45RA+CD27+ CD4 cells, and may be involved in suppressor activity of these cells at least in part via its effects on cAMP production.
Sugita
K
K
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Hirose
T
T
Rothstein
D M
DM
Donahue
C
C
Schlossman
S F
SF
Morimoto
C
C
D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000242:Cyclic AMP; D017493:Leukocyte Common Antigens