Deficiency of CD11b or CD11d results in reduced staphylococcal enterotoxin-induced T cell response and T cell phenotypic changes.
The beta(2) integrin CD11a is involved in T cell-APC interactions, but the roles of CD11b, CD11c, and CD11d in such interactions have not been examined. To evaluate the roles of each CD11/CD18 integrin in T cell-APC interactions, we tested the ability of splenocytes of CD11-knockout (KO) mice to respond to staphylococcal enterotoxins (SEs), a commonly used superantigen. The defect in T cell proliferation with SEA was more severe in splenocytes from mice deficient in CD18, CD11b, or CD11d than in CD11a-deficient splenocytes, with a normal response in CD11c-deficient splenocytes. Mixing experiments showed that the defect of both CD11b-KO and CD11d-KO splenocytes was, unexpectedly, in T cells rather than in APC. Cytometric analysis failed to detect CD11b or CD11d on resting or activated T cells or on thymocytes of wild-type adult mice, nor did Abs directed to these integrins block responses in culture, suggesting that T cells educated in CD11b-KO or CD11d-KO mice were phenotypically altered. Consistent with this hypothesis, T cells from CD11b-KO and CD11d-KO splenocytes exhibited reduced intensity of CD3 and CD28 expression and decreased ratios of CD4/CD8 cells, and CD4(+) T cells were reduced among CD11b-KO and CD11d-KO thymocytes. CD11b and CD11d were coexpressed on a subset of early wild-type fetal thymocytes. We postulate that transient thymocyte expression of both CD11b and CD11d is nonredundantly required for normal thymocyte and T cell development, leading to phenotypic changes in T cells that result in the reduced response to SE stimulation.
Wu
Huaizhu
H
Section of Atherosclerosis, Department of Medicine, Baylor College of Medicine, 6565 Fannin, Houston, TX 77030, USA.
Rodgers
John R
JR
Perrard
Xiao-Yuan Dai
XY
Perrard
Jerry L
JL
Prince
Joseph E
JE
Abe
Yasunori
Y
Davis
Beckley K
BK
Dietsch
Greg
G
Smith
C Wayne
CW
Ballantyne
Christie M
CM
D000818:Animals; D018845:CD11 Antigens / Q000032:analysis / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000276:immunology; D005434:Flow Cytometry; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000032:analysis / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018845:CD11 Antigens; D039481:CD11b Antigen; D018821:CD18 Antigens; D004768:Enterotoxins; C406812:ITGAD protein, human; D039001:Integrin alpha Chains; D018089:Superantigens; C049463:enterotoxin E, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate