CD8beta/CD28 expression defines functionally distinct populations of peripheral blood T lymphocytes.
Peripheral blood CD8+ T lymphocytes generally express the CD8 coreceptor as an alphabeta heterodimer. On these cells, the CD8beta chain is present either at high (CD8betahigh) or low density (CD8betalow). CD8betahigh cells are CD28+, whereas CD8betalow cells are CD28+ or CD28-. Therefore, three subpopulations of CD8+ T cells can be described: (i) CD8betahighCD28+ (ii) CD8betalowCD28+, and (iii) CD8betalowCD28- cells. Phenotypic and functional characterization of these CD8+ T cell subsets revealed significant differences. CD8betahighCD28+ cells predominantly express CD45RA. In contrast, CD8betalowCD28+ cells frequently express CD45R0 and the activating NK receptor CD161. CD8betalowCD28- cells frequently revert to the CD45RA phenotype. In addition, these cells express CD16, CD56, CD94, and the killer-inhibitory receptors NKB1 and CD158a. Intracellular IL-2 was frequently detected in CD8betahighCD28+ cells and CD8betalowCD28+ cells, but not CD8betalowCD28- cells. CD8betalowCD28+ cells and CD8betalowCD28- cells frequently stained positive for IFN-gamma. In addition, these cells contain intracellular perforin and granzyme A. Expression of Fas (CD95) as well as susceptibility to apoptosis is markedly increased in CD8betalowCD28+ and CD8betalowCD28- cells as compared to CD8betahighCD28+ cells. In vitro activation of peripheral blood lymphocytes triggered expansion of CD8betahighCD28+ cells as well as a development into CD8betalowCD28+ and CD8betalowCD28- cells. Similarly, activation of CD8betahighCD28+ cord blood cells resulted in the appearance of CD8betalowCD28+ and CD8betalowCD28- cells. These data suggest that CD8betahighCD28+ cells can differentiate into CD8betalowCD28+ and CD8betalowCD28- cells upon TCR stimulation. Therefore, the CD8beta/CD28 subsets in peripheral blood may reflect distinct stages of post-thymic CD8+T cell development.
Werwitzke
S
S
Departments of Clinical Immunology and Haematology and Oncology, Hannover Medical School, Hannover, Germany.
Tiede
A
A
Drescher
B E
BE
Schmidt
R E
RE
Witte
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018106:CD28 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018106:CD28 Antigens; D016827:CD8 Antigens; C477867:CD8beta antigen; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens