IL-2-dependent expansion of CD3+ large granular lymphocytes expressing T cell receptor-gamma delta. Evidence for a functional receptor by anti-CD3 activation of cytolysis.
The nature and function of the TCR on PBL of a patient with a chronic CD3+ large granular (LGL) proliferation was studied. Fresh peripheral blood from this individual was comprised of 80% lymphocytes, 65 to 75% of which were CD3+, CD8+, Leu-7+ LGL. Of these LGL, 72% initially expressed the TCR-alpha beta heterodimer, whereas 21% did not. Cytotoxicity directed against MHC-unrestricted targets was minimal. After several days of exposure to rIL-2, cytotoxic activity was greatly enhanced, correlating with a disappearance of CD3+ cells expressing the alpha beta heterodimer. Twelve days after rIL-2 exposure, the LGL expressed only TCR-gamma delta heterodimer in association with CD3 and alpha beta heterodimer expression could no longer be detected. The TCR/CD3 complex on these cells was demonstrated to be functional as anti-CD3 elicited an increase in cytoplasmic free calcium concentration, stimulated cytolytic activity, and stimulated granule enzyme secretion from the LGL.
Colamonici
O R
OR
Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892.
Ang
S
S
Quinones
R
R
Henkart
P
P
Heikkila
R
R
Gress
R
R
Felix
C
C
Kirsch
I
I
Longo
D
D
Marti
G
G
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D008214:Lymphocytes / Q000032:analysis* / Q000276:immunology / Q000473:pathology; D008218:Lymphocytosis / Q000473:pathology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D002118:Calcium