Differentiation of Ia-reactive CD8+ murine T cells does not require Ia engagement. Implications for the role of CD4 and CD8 accessory molecules in T cell differentiation.
The present study was undertaken to assess the Ia differentiation requirements of CD8+ class II-allospecific CTL, whose CD8+ phenotype is apparently "discordant" with their MHC class II reactivity. To do so, we compared the effect of in vivo anti-Ia blockade on the differentiation of Ia-reactive CD8+ CTL with its effect on the differentiation of CD4+ T cells. We found that anti-Ia blockade did not detectably interfere with the differentiation of CD8+ Ia-reactive CTL, even though it arrested the differentiation of CD4+ T cells. Thus, the differentiation of CD4+ T cells is strictly dependent upon Ia engagement, whereas the differentiation of CD8+ T cells, even those with reactivity against MHC class II alloantigens, does not require Ia engagement. These results support the concept that Ia-reactive CD8+ T cells are conventional CD8+ CTL, probably selected by self-class I MHC molecules during differentiation, whose receptors fortuitously crossreact on MHC class II alloantigens. Taken together, the present data indicate an intimate relationship between CD4/CD8 expression with MHC class specificity during T cell differentiation and selection. We suggest that an active triggering role for CD4 and CD8 accessory molecules in T cell differentiation is best able to explain these observations.
Mizuochi
T
T
Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Tentori
L
L
Sharrow
S O
SO
Kruisbeek
A M
AM
Singer
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002454:Cell Differentiation; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007116:Immunization, Passive; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II