CD2-CD4-CD8- lymph node T lymphocytes in MRL lpr/lpr mice are derived from a CD2+CD4+CD8+ thymic precursor.
MRL lpr/lpr (lymphoproliferative, lpr) mice demonstrate an age-dependent lymphoproliferation and development of autoimmunity. Characteristic of the lymphoproliferation in these mice is the accumulation of large numbers of CD4-CD8-(CD4-8-),CD3+ T lymphocytes in their lymph nodes. The development of the CD4-8- cells, which also aberrantly express B220 and CD44 (Pgp-1) but are CD2-, has been shown to be thymus dependent. An unusual feature of lpr CD4-8-T lymphocytes is that although they appear unresponsive to stimulation, as defined by proliferation and IL-2 production, they have undergone thymic negative selection. As thymic deletion normally occurs at the CD4+CD8+ (CD4+8+) stage, this raises the dilemma that lpr CD4-8- T lymphocytes have either previously been CD4+8+, or they are able to undergo thymic selection as CD4-8- cells. We have addressed this question by examining the methylation status of the CD8 gene in MRL lpr CD4-8- lymph node cells. Demethylation of the CD8 gene has been shown to be an indicator of previous CD8 expression. We find that the CD8 gene in lpr CD4-8- lymph node cells, as well as in the abnormal B220+ CD4-8- lpr thymocytes, is demethylated, suggesting that these cells have previously expressed CD8. In addition, we find that the lpr CD4+8+ thymocyte population contains an increased percentage of atypical B220+, CD44+ cells that are virtually all CD2+. Taken together, these data are consistent with the lpr CD2-CD4-8- population of LNC having arisen from a CD2+ CD4+8+ thymic stage of differentiation.
Landolfi
M M
MM
Department of Medicine, Stanford University Medical School, CA 94305-5487.
Van Houten
N
N
Russell
J Q
JQ
Scollay
R
R
Parnes
J R
JR
Budd
R C
RC
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis / Q000235:genetics; D003640:Dealkylation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D051381:Rats; D011971:Receptors, Immunologic / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D017493:Leukocyte Common Antigens